TY - JOUR AU - Ciaglia, T. AU - Vestuto, V. AU - Bertamino, A. AU - González-Muñiz, R. AU - Gómez-Monterrey, I. TI - On the modulation of TRPM channels: Current perspectives and anticancer therapeutic implications JF - FRONTIERS IN ONCOLOGY J2 - FRONT ONCOL VL - 12 PY - 2023 SN - 2234-943X DO - 10.3389/fonc.2022.1065935 UR - https://m2.mtmt.hu/api/publication/33687612 ID - 33687612 N1 - Dipartimento di Farmacia (DIFARMA), Università degli Studi di Salerno, Fisciano, Italy Departamento de Biomiméticos, Instituto de Química Médica, Madrid, Spain Dipartimento di Farmacia, Università degli Studi di Napoli “Federico II”, Naples, Italy Export Date: 8 March 2023 Correspondence Address: González-Muñiz, R.; Departamento de Biomiméticos, Spain; email: iqmg313@iqm.csic.es Correspondence Address: Gómez-Monterrey, I.; Dipartimento di Farmacia, Italy; email: imgomez@unina.it Funding details: Ministerio de Ciencia e Innovación, MICINN, PID2021-126423OB-C22, RTI2018-097189B-C22 Funding text 1: This work was supported by grants from Regione Campania-PON Campania FESR 2014-2020 “Combattere la resistenza tumorale: piattaforma integrate multidisciplinare per un approccio tecnologico innovativo alle oncoterapie-Campania Oncoterapie (Project N. B61G18000470007), and Spanish Ministry of Science and Innovation (RTI2018-097189B-C22 and PID2021-126423OB-C22). AB - The transient melastatin receptor potential (TRPM) ion channel subfamily functions as cellular sensors and transducers of critical biological signal pathways by regulating ion homeostasis. Some members of TRPM have been cloned from cancerous tissues, and their abnormal expressions in various solid malignancies have been correlated with cancer cell growth, survival, or death. Recent evidence also highlights the mechanisms underlying the role of TRPMs in tumor epithelial-mesenchymal transition (EMT), autophagy, and cancer metabolic reprogramming. These implications support TRPM channels as potential molecular targets and their modulation as an innovative therapeutic approach against cancer. Here, we discuss the general characteristics of the different TRPMs, focusing on current knowledge about the connection between TRPM channels and critical features of cancer. We also cover TRPM modulators used as pharmaceutical tools in biological trials and an indication of the only clinical trial with a TRPM modulator about cancer. To conclude, the authors describe the prospects for TRPM channels in oncology. Copyright © 2023 Ciaglia, Vestuto, Bertamino, González-Muñiz and Gómez-Monterrey. LA - English DB - MTMT ER - TY - JOUR AU - Liu, Yusheng AU - Lyu, Yihan AU - Zhu, Lijuan AU - Wang, Hongmei TI - Role of TRP Channels in Liver-Related Diseases JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 15 PG - 28 SN - 1661-6596 DO - 10.3390/ijms241512509 UR - https://m2.mtmt.hu/api/publication/34176591 ID - 34176591 N1 - Department of Pharmacology, School of Medicine, Southeast University, Nanjing, 210009, China Key Laboratory of Developmental Genes and Human Diseases, MOE, Department of Histology and Embryology, School of Medicine, Southeast University, Nanjing, 210009, China Export Date: 5 October 2023 Correspondence Address: Wang, H.; Department of Pharmacology, China; email: 101012573@seu.edu.cn AB - The liver plays a crucial role in preserving the homeostasis of an entire organism by metabolizing both endogenous and exogenous substances, a process that relies on the harmonious interactions of hepatocytes, hepatic stellate cells (HSCs), Kupffer cells (KCs), and vascular endothelial cells (ECs). The disruption of the liver's normal structure and function by diverse pathogenic factors imposes a significant healthcare burden. At present, most of the treatments for liver disease are palliative in nature, rather than curative or restorative. Transient receptor potential (TRP) channels, which are extensively expressed in the liver, play a crucial role in regulating intracellular cation concentration and serve as the origin or intermediary stage of certain signaling pathways that contribute to liver diseases. This review provides an overview of recent developments in liver disease research, as well as an examination of the expression and function of TRP channels in various liver cell types. Furthermore, we elucidate the molecular mechanism by which TRP channels mediate liver injury, liver fibrosis, and hepatocellular carcinoma (HCC). Ultimately, the present discourse delves into the current state of research and extant issues pertaining to the targeting of TRP channels in the treatment of liver diseases and other ailments. Despite the numerous obstacles encountered, TRP channels persist as an extremely important target for forthcoming clinical interventions aimed at treating liver diseases. LA - English DB - MTMT ER - TY - JOUR AU - Maliougina, M. AU - El, Hiani Y. TI - TRPM2: bridging calcium and ROS signaling pathways—implications for human diseases JF - FRONTIERS IN PHYSIOLOGY J2 - FRONT PHYSIOL VL - 14 PY - 2023 SN - 1664-042X DO - 10.3389/fphys.2023.1217828 UR - https://m2.mtmt.hu/api/publication/34125124 ID - 34125124 N1 - Export Date: 4 September 2023 Correspondence Address: El Hiani, Y.; Department of Physiology and Biophysics, Canada; email: yassine.elhiani@dal.ca Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; calcium ion, 14127-61-8; cisplatin, 15663-27-1, 26035-31-4, 96081-74-2; docetaxel, 114977-28-5; doxorubicin, 23214-92-8, 25316-40-9; fluorouracil, 51-21-8; glutamic acid, 11070-68-1, 138-15-8, 56-86-0, 6899-05-4; paclitaxel, 33069-62-4; tamoxifen, 10540-29-1 Funding details: Research Nova Scotia, RNS, MED-EST-2019-2174 Funding text 1: This work was supported by the ResearchNS- MED-EST-2019-2174 to YE. AB - TRPM2 is a versatile and essential signaling molecule that plays diverse roles in Ca2+ homeostasis and oxidative stress signaling, with implications in various diseases. Research evidence has shown that TRPM2 is a promising therapeutic target. However, the decision of whether to activate or inhibit TRPM2 function depends on the context and specific disease. A deeper understanding of the molecular mechanisms governing TRPM2 activation and regulation could pave the way for the development of innovative therapeutics targeting TRPM2 to treat a broad range of diseases. In this review, we examine the structural and biophysical details of TRPM2, its involvement in neurological and cardiovascular diseases, and its role in inflammation and immune system function. In addition, we provide a comprehensive overview of the current knowledge of TRPM2 signaling pathways in cancer, including its functions in bioenergetics, oxidant defense, autophagy, and response to anticancer drugs. Copyright © 2023 Maliougina and El Hiani. LA - English DB - MTMT ER - TY - JOUR AU - Okada, Y. AU - Numata, T. AU - Sabirov, R.Z. AU - Kashio, M. AU - Merzlyak, P.G. AU - Sato-Numata, K. TI - Cell death induction and protection by activation of ubiquitously expressed anion/cation channels. Part 3: the roles and properties of TRPM2 and TRPM7 JF - FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY J2 - FRONT CELL DEV BIOL VL - 11 PY - 2023 SN - 2296-634X DO - 10.3389/fcell.2023.1246955 UR - https://m2.mtmt.hu/api/publication/34221622 ID - 34221622 N1 - Export Date: 27 October 2023 Correspondence Address: Okada, Y.; National Institute for Physiological Sciences (NIPS)Japan; email: okada@nips.ac.jp AB - Cell volume regulation (CVR) is a prerequisite for animal cells to survive and fulfill their functions. CVR dysfunction is essentially involved in the induction of cell death. In fact, sustained normotonic cell swelling and shrinkage are associated with necrosis and apoptosis, and thus called the necrotic volume increase (NVI) and the apoptotic volume decrease (AVD), respectively. Since a number of ubiquitously expressed ion channels are involved in the CVR processes, these volume-regulatory ion channels are also implicated in the NVI and AVD events. In Part 1 and Part 2 of this series of review articles, we described the roles of swelling-activated anion channels called VSOR or VRAC and acid-activated anion channels called ASOR or PAC in CVR and cell death processes. Here, Part 3 focuses on therein roles of Ca2+-permeable non-selective TRPM2 and TRPM7 cation channels activated by stress. First, we summarize their phenotypic properties and molecular structure. Second, we describe their roles in CVR. Since cell death induction is tightly coupled to dysfunction of CVR, third, we focus on their participation in the induction of or protection against cell death under oxidative, acidotoxic, excitotoxic, and ischemic conditions. In this regard, we pay attention to the sensitivity of TRPM2 and TRPM7 to a variety of stress as well as to their capability to physicall and functionally interact with other volume-related channels and membrane enzymes. Also, we summarize a large number of reports hitherto published in which TRPM2 and TRPM7 channels are shown to be involved in cell death associated with a variety of diseases or disorders, in some cases as double-edged swords. Lastly, we attempt to describe how TRPM2 and TRPM7 are organized in the ionic mechanisms leading to cell death induction and protection. Copyright © 2023 Okada, Numata, Sabirov, Kashio, Merzlyak and Sato-Numata. LA - English DB - MTMT ER - TY - JOUR AU - Ehrlich, Wiebke AU - Gahan, James M. AU - Rentzsch, Fabian AU - Kuehn, Frank J. P. TI - TRPM2 causes sensitization to oxidative stress but attenuates high-temperature injury in the sea anemone Nematostella vectensis JF - JOURNAL OF EXPERIMENTAL BIOLOGY J2 - J EXP BIOL VL - 225 PY - 2022 IS - 6 SP - 43717 EP - 43717 PG - 14 SN - 0022-0949 DO - 10.1242/jeb.243717 UR - https://m2.mtmt.hu/api/publication/33318846 ID - 33318846 AB - In humans, the cation channel TRPM2 (HsTRPM2) has been intensively studied because it is involved in oxidative stress-mediated apoptosis and also contributes to temperature regulation. The gating mechanism of TRPM2 is quite complex, with a C-terminally localized enzyme domain playing a crucial role. The analysis of orthologues of TRPM2, in particular from the distantly related marine invertebrate Nematostella vectensis (NvTRPM2), revealed that during evolution, the functional role of the endogenous enzyme domain of TRPM2 has undergone fundamental changes. In this study, we investigated whether these evolutionary differences also apply to the physiological functions of TRPM2. For this purpose, we generated a TRPM2 loss-offunction mutation in N. vectensis and compared the phenotypes of wild-type and mutant animals after exposure to either oxidative stress or high temperature. Our results show that under standard culture conditions, mutant animals are indistinguishable from wild-type animals in terms of morphology and development. However, exposure of the two experimental groups to different stressors revealed that TRPM2 causes sensitization to oxidative stress but attenuates high-temperature injury in N. vectensis. Therefore, NvTRPM2 plays opposite roles in the cellular response to these two different stressors. These findings reveal a similar physiological spectrum of activity of TRPM2 in humans and N. vectensis and open up the possibility of establishing N. vectensis as a model organism for the physiological function of TRPM2. LA - English DB - MTMT ER - TY - JOUR AU - Sander, S. AU - Pick, J. AU - Gattkowski, E. AU - Fliegert, R. AU - Tidow, H. TI - The crystal structure of TRPM2 MHR1/2 domain reveals a conserved Zn2+-binding domain essential for structural integrity and channel activity JF - PROTEIN SCIENCE J2 - PROTEIN SCI VL - 31 PY - 2022 IS - 6 SN - 0961-8368 DO - 10.1002/pro.4320 UR - https://m2.mtmt.hu/api/publication/33063833 ID - 33063833 N1 - Hamburg Advanced Research Centre for Bioorganic Chemistry (HARBOR) & Department of Chemistry, Institute for Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Export Date: 24 August 2022 CODEN: PRCIE Correspondence Address: Tidow, H.; Hamburg Advanced Research Centre for Bioorganic Chemistry (HARBOR) & Department of Chemistry, Germany; email: tidow@chemie.uni-hamburg.de Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; calcium, 7440-70-2, 14092-94-5; zinc, 7440-66-6, 14378-32-6; Adenosine Diphosphate Ribose; Calcium; TRPM Cation Channels; Zinc Funding details: European Molecular Biology Laboratory, EMBL Funding details: Deutsche Forschungsgemeinschaft, DFG, SFB1328 Funding text 1: The authors are grateful to the staff at beamlines P14 and P13 (EMBL, Hamburg) and thank members of the Tidow and Fliegert labs for helpful discussions. The authors acknowledge access to the Sample Preparation and Characterization (SPC) Facility of EMBL, Hamburg. This work was supported by the Deutsche Forschungsgemeinschaft (DFG) (SFB1328, project A05 to Henning Tidow and Ralf Fliegert). Open Access funding enabled and organized by Projekt DEAL. Funding text 2: The authors are grateful to the staff at beamlines P14 and P13 (EMBL, Hamburg) and thank members of the Tidow and Fliegert labs for helpful discussions. The authors acknowledge access to the Sample Preparation and Characterization (SPC) Facility of EMBL, Hamburg. This work was supported by the Deutsche Forschungsgemeinschaft (DFG) (SFB1328, project A05 to Henning Tidow and Ralf Fliegert). Open Access funding enabled and organized by Projekt DEAL. AB - Transient receptor potential melastatin 2 (TRPM2) is a Ca2+-permeable, nonselective cation channel involved in diverse physiological processes such as immune response, apoptosis, and body temperature sensing. TRPM2 is activated by ADP-ribose (ADPR) and 2′-deoxy-ADPR in a Ca2+-dependent manner. While two distinct binding sites exist for ADPR that exert different functions dependent on the species, the involvement of either binding site regarding the superagonistic effect of 2′-deoxy-ADPR is not clear yet. Here, we report the crystal structure of the MHR1/2 domain of TRPM2 from zebrafish (Danio rerio), and show that both ligands bind to this domain and activate the channel. We identified a so far unrecognized Zn2+-binding domain that was not resolved in previous cryo-EM structures and that is conserved in most TRPM channels. In combination with patch clamp experiments we comprehensively characterize the effect of the Zn2+-binding domain on TRPM2 activation. Our results provide insight into a conserved motif essential for structural integrity and channel activity. © 2022 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society. LA - English DB - MTMT ER - TY - JOUR AU - Zong, P. AU - Lin, Q. AU - Feng, J. AU - Yue, L. TI - A Systemic Review of the Integral Role of TRPM2 in Ischemic Stroke: From Upstream Risk Factors to Ultimate Neuronal Death JF - CELLS J2 - CELLS-BASEL VL - 11 PY - 2022 IS - 3 SN - 2073-4409 DO - 10.3390/cells11030491 UR - https://m2.mtmt.hu/api/publication/32657389 ID - 32657389 N1 - Department of Cell Biology, Calhoun Cardiology Center, University of Connecticut School of Medicine (UConnHealth), Farmington, CT 06030, United States Department of Ecology and Evolutionary Biology, University of Connecticut, StorrsCT 06269, United States Export Date: 9 February 2022 Correspondence Address: Yue, L.; Department of Cell Biology, United States; email: lyue@uchc.edu Funding details: National Institutes of Health, NIH, R01-HL143750 Funding details: American Heart Association, AHA, 19TPA34890022 Funding text 1: Acknowledgments: This work was partially supported by the National Institute of Health (R01-HL143750) and American Heart Association (19TPA34890022) to LY. Funding text 2: Funding: This research was funded by National Institute of Health [R01-HL143750] and American Heart Association [19TPA34890022]. And The APC was funded by National Institute of Health. AB - Ischemic stroke causes a heavy health burden worldwide, with over 10 million new cases every year. Despite the high prevalence and mortality rate of ischemic stroke, the underlying molecular mechanisms for the common etiological factors of ischemic stroke and ischemic stroke itself remain unclear, which results in insufficient preventive strategies and ineffective treatments for this devastating disease. In this review, we demonstrate that transient receptor potential cation channel, subfamily M, member 2 (TRPM2), a non-selective ion channel activated by oxidative stress, is actively involved in all the important steps in the etiology and pathology of ischemic stroke. TRPM2 could be a promising target in screening more effective prophylactic strategies and therapeutic medications for ischemic stroke. © 2022 by the authors. Licensee MDPI, Basel, Switzerland. LA - English DB - MTMT ER - TY - JOUR AU - Gattkowski, E. AU - Rutherford, T.J. AU - Möckl, F. AU - Bauche, A. AU - Sander, S. AU - Fliegert, R. AU - Tidow, H. TI - Analysis of ligand binding and resulting conformational changes in pyrophosphatase NUDT9 JF - FEBS JOURNAL J2 - FEBS J PY - 2021 SN - 1742-464X DO - 10.1111/febs.16097 UR - https://m2.mtmt.hu/api/publication/32188279 ID - 32188279 N1 - The Hamburg Advanced Research Center for Bioorganic Chemistry (HARBOR) & Department of Chemistry, Institute for Biochemistry and Molecular Biology, University of Hamburg, Germany MRC Laboratory of Molecular Biology, Cambridge, United Kingdom Department of Biochemistry and Molecular Cell Biology, University Medical Centre Hamburg-Eppendorf, Germany Export Date: 10 September 2021 CODEN: FJEOA Correspondence Address: Tidow, H.; The Hamburg Advanced Research Center for Bioorganic Chemistry (HARBOR) & Department of Chemistry, Germany; email: tidow@chemie.uni-hamburg.de Funding details: SFB1328 Funding details: Deutsche Forschungsgemeinschaft, DFG, EXC 1074 Funding text 1: We thank members of the Fliegert and Tidow laboratories for helpful discussions. The synchrotron SAXS data were collected at beamline P12 operated by EMBL Hamburg at the PETRA III storage ring (DESY, Hamburg, Germany). We acknowledge access to the Sample Preparation and Characterization (SPC) Facility of EMBL (Hamburg). This research was funded by the Collaborative Research Centre SFB1328 and the excellence cluster ‘The Hamburg Centre for Ultrafast Imaging ‐ Structure, Dynamics and Control of Matter at the Atomic Scale’ of the Deutsche Forschungsgemeinschaft (DFG EXC 1074). The Hamburg Advanced Research Center for Bioorganic Chemistry (HARBOR) & Department of Chemistry, Institute for Biochemistry and Molecular Biology, University of Hamburg, Germany MRC Laboratory of Molecular Biology, Cambridge, United Kingdom Department of Biochemistry and Molecular Cell Biology, University Medical Centre Hamburg-Eppendorf, Germany Export Date: 13 September 2021 CODEN: FJEOA Correspondence Address: Tidow, H.; The Hamburg Advanced Research Center for Bioorganic Chemistry (HARBOR) & Department of Chemistry, Germany; email: tidow@chemie.uni-hamburg.de Funding details: SFB1328 Funding details: Deutsche Forschungsgemeinschaft, DFG, EXC 1074 Funding text 1: We thank members of the Fliegert and Tidow laboratories for helpful discussions. The synchrotron SAXS data were collected at beamline P12 operated by EMBL Hamburg at the PETRA III storage ring (DESY, Hamburg, Germany). We acknowledge access to the Sample Preparation and Characterization (SPC) Facility of EMBL (Hamburg). This research was funded by the Collaborative Research Centre SFB1328 and the excellence cluster ‘The Hamburg Centre for Ultrafast Imaging ‐ Structure, Dynamics and Control of Matter at the Atomic Scale’ of the Deutsche Forschungsgemeinschaft (DFG EXC 1074). AB - Nudix hydrolase 9 (NUDT9) is a member of the nucleoside linked to another moiety X (NUDIX) protein superfamily, which hydrolyses a broad spectrum of organic pyrophosphates from metabolic processes. ADP-ribose (ADPR) has been the only known endogenous substrate accepted by NUDT9 so far. The Ca2+-permeable transient receptor potential melastatin subfamily 2 (TRPM2) channel contains a homologous NUDT9-homology (NUDT9H) domain and is activated by ADPR. Sustained Ca2+ influx via ADPR-activated TRPM2 triggers apoptotic mechanisms. Thus, a precise regulation of cellular ADPR levels by NUDT9 is essential. A detailed characterization of the enzyme-substrate interaction would help to understand the high substrate specificity of NUDT9. Here, we analysed ligand binding to NUDT9 using a variety of biophysical techniques. We identified 2′-deoxy-ADPR as an additional substrate for NUDT9. Similar enzyme kinetics and binding affinities were determined for the two ligands. The high-affinity binding was preserved in NUDT9 containing the mutated NUDIX box derived from the human NUDT9H domain. NMR spectroscopy indicated that ADPR and 2′-deoxy-ADPR bind to the same binding site of NUDT9. Backbone resonance assignment and subsequent molecular docking allowed further characterization of the binding pocket. Substantial conformational changes of NUDT9 upon ligand binding were observed which might allow for the development of NUDT9-based ADPR fluorescence resonance energy transfer sensors that may help with the analysis of ADPR signalling processes in cells in the future. © 2021 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies LA - English DB - MTMT ER - TY - JOUR AU - Morad, H. AU - Luqman, S. AU - Tan, C.-H. AU - Swann, V. AU - McNaughton, P.A. TI - TRPM2 ion channels steer neutrophils towards a source of hydrogen peroxide JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 11 PY - 2021 IS - 1 SN - 2045-2322 DO - 10.1038/s41598-021-88224-5 UR - https://m2.mtmt.hu/api/publication/32053849 ID - 32053849 N1 - Wolfson Centre for Age-Related Diseases, King’s College London, Guy’s Campus, London Bridge, London, SE1 1UL, United Kingdom CSIR-Central Institute of Medicinal and Aromatic Plants, Uttar Pradesh, Lucknow, 226015, India Department of Neurology, Kaohsiung Medical University Hospital, and Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom Export Date: 3 June 2021 Correspondence Address: McNaughton, P.A.; Wolfson Centre for Age-Related Diseases, Guy’s Campus, London Bridge, United Kingdom; email: peter.mcnaughton@kcl.ac.uk Funding details: Wellcome Trust, WT Funding details: Department of Health Research, India, DHR Funding text 1: Supported by grant number 205006/Z/16/Z from the Wellcome Trust to PMcN and by a KCL Biomedical Research Centre PhD studentship to HM. SL acknowledges the Department of Health Research (DHR), Ministry of Health & Family Welfare, Government of India for awarding a Long-Term Fellowship at KCL, UK. We thank Dr Larissa Pinto for assistance with histochemistry and Dr Lucy Norling and Professor Mauro Perretti for supplying human blood neutrophils. Wolfson Centre for Age-Related Diseases, King’s College London, Guy’s Campus, London Bridge, London, SE1 1UL, United Kingdom CSIR-Central Institute of Medicinal and Aromatic Plants, Uttar Pradesh, Lucknow, 226015, India Department of Neurology, Kaohsiung Medical University Hospital, and Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom Export Date: 10 September 2021 Correspondence Address: McNaughton, P.A.; Wolfson Centre for Age-Related Diseases, Guy’s Campus, London Bridge, United Kingdom; email: peter.mcnaughton@kcl.ac.uk Funding details: Wellcome Trust, WT, 205006/Z/16/Z Funding details: Department of Health Research, India, DHR Funding text 1: Supported by grant number 205006/Z/16/Z from the Wellcome Trust to PMcN and by a KCL Biomedical Research Centre PhD studentship to HM. SL acknowledges the Department of Health Research (DHR), Ministry of Health & Family Welfare, Government of India for awarding a Long-Term Fellowship at KCL, UK. We thank Dr Larissa Pinto for assistance with histochemistry and Dr Lucy Norling and Professor Mauro Perretti for supplying human blood neutrophils. Wolfson Centre for Age-Related Diseases, King’s College London, Guy’s Campus, London Bridge, London, SE1 1UL, United Kingdom CSIR-Central Institute of Medicinal and Aromatic Plants, Uttar Pradesh, Lucknow, 226015, India Department of Neurology, Kaohsiung Medical University Hospital, and Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom Export Date: 13 September 2021 Correspondence Address: McNaughton, P.A.; Wolfson Centre for Age-Related Diseases, Guy’s Campus, London Bridge, United Kingdom; email: peter.mcnaughton@kcl.ac.uk Funding details: Wellcome Trust, WT, 205006/Z/16/Z Funding details: Department of Health Research, India, DHR Funding text 1: Supported by grant number 205006/Z/16/Z from the Wellcome Trust to PMcN and by a KCL Biomedical Research Centre PhD studentship to HM. SL acknowledges the Department of Health Research (DHR), Ministry of Health & Family Welfare, Government of India for awarding a Long-Term Fellowship at KCL, UK. We thank Dr Larissa Pinto for assistance with histochemistry and Dr Lucy Norling and Professor Mauro Perretti for supplying human blood neutrophils. AB - Neutrophils must navigate accurately towards pathogens in order to destroy invaders and thus defend our bodies against infection. Here we show that hydrogen peroxide, a potent neutrophil chemoattractant, guides chemotaxis by activating calcium-permeable TRPM2 ion channels and generating an intracellular leading-edge calcium “pulse”. The thermal sensitivity of TRPM2 activation means that chemotaxis towards hydrogen peroxide is strongly promoted by small temperature elevations, suggesting that an important function of fever may be to enhance neutrophil chemotaxis by facilitating calcium influx through TRPM2. Chemotaxis towards conventional chemoattractants such as LPS, CXCL2 and C5a does not depend on TRPM2 but is driven in a similar way by leading-edge calcium pulses. Other proposed initiators of neutrophil movement, such as PI3K, Rac and lyn, influence chemotaxis by modulating the amplitude of calcium pulses. We propose that intracellular leading-edge calcium pulses are universal drivers of the motile machinery involved in neutrophil chemotaxis. © 2021, The Author(s). LA - English DB - MTMT ER - TY - JOUR AU - Szöllősi, András TI - Two decades of evolution of our understanding of the transient receptor potential melastatin 2 (Trpm2) cation channel JF - LIFE-BASEL J2 - LIFE-BASEL VL - 11 PY - 2021 IS - 5 PG - 23 SN - 2075-1729 DO - 10.3390/life11050397 UR - https://m2.mtmt.hu/api/publication/32040119 ID - 32040119 N1 - Department of Medical Biochemistry, Semmelweis University, Budapest, 1085, Hungary MTA-SE Lendület Ion Channel Research Group, Semmelweis University, Budapest, 1085, Hungary HCEMM-SE Molecular Channelopathies Research Group, Semmelweis University, Budapest, 1085, Hungary Cited By :2 Export Date: 9 March 2022 Correspondence Address: Szollosi, A.; Department of Medical Biochemistry, Hungary; email: szollosi.andras@med.semmelweis-univ.hu Funding details: 739593 Funding details: LP2017-14/2017 Funding text 1: Supported by MTA Lend?let grant LP2017-14/2017 and EU Horizon 2020 Research and Innovation Program grant 739593. Funding text 2: Funding: Supported by MTA Lendület grant LP2017-14/2017 and EU Horizon 2020 Research and Innovation Program grant 739593. AB - The transient receptor potential melastatin (TRPM) family belongs to the superfamily of TRP ion channels. It consists of eight family members that are involved in a plethora of cellular functions. TRPM2 is a homotetrameric Ca2+-permeable cation channel activated upon oxidative stress and is important, among others, for body heat control, immune cell activation and insulin secretion. Invertebrate TRPM2 proteins are channel enzymes; they hydrolyze the activating ligand, ADP-ribose, which is likely important for functional regulation. Since its cloning in 1998, the understanding of the biophysical properties of the channel has greatly advanced due to a vast number of structure– function studies. The physiological regulators of the channel have been identified and characterized in cell-free systems. In the wake of the recent structural biochemistry revolution, several TRPM2 cryo-EM structures have been published. These structures have helped to understand the general features of the channel, but at the same time have revealed unexplained mechanistic differences among channel orthologues. The present review aims at depicting the major research lines in TRPM2 structure-function. It discusses biophysical properties of the pore and the mode of action of direct channel effectors, and interprets these functional properties on the basis of recent three-dimensional structural models. © 2021 by the author. Licensee MDPI, Basel, Switzerland. LA - English DB - MTMT ER - TY - JOUR AU - Baszczyňski, O. AU - Watt, J.M. AU - Rozewitz, M.D. AU - Fliegert, R. AU - Guse, A.H. AU - Potter, B.V.L. TI - Synthesis of phosphonoacetate analogues of the second messenger adenosine 5′-diphosphate ribose (ADPR) JF - RSC ADVANCES J2 - RSC ADV VL - 10 PY - 2020 IS - 3 SP - 1776 EP - 1785 PG - 10 SN - 2046-2069 DO - 10.1039/c9ra09284f UR - https://m2.mtmt.hu/api/publication/31258315 ID - 31258315 N1 - Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, United Kingdom Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, United Kingdom Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center, Hamburg-Eppendorf Martinistrasse 52, Hamburg, 20246, Germany Export Date: 24 March 2020 CODEN: RSCAC Correspondence Address: Potter, B.V.L.; Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, United Kingdom; email: barry.potter@pharm.ox.ac.uk Funding details: European Commission, EU, DLV-813284 Funding details: Deutsche Forschungsgemeinschaft, DFG, SFB1328, 335447717 Funding details: Wellcome Trust, WT Funding text 1: This work was supported by the Deutsche For-schungsgemeinscha (DFG) (Project number 335447717; SFB1328, project A01 to A. H. G, SFB1328, project A05 to R. F) and the Wellcome Trust. BVLP is a Wellcome Trust Senior Investigator (Grant 101010). Research in the Guse/Fliegert labs is also supported by the Joachim-Herz-Foundation, Infecto-physics consortium, project 4; and EU project INTEGRATA - DLV-813284. Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, United Kingdom Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, United Kingdom Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center, Hamburg-Eppendorf Martinistrasse 52, Hamburg, 20246, Germany Export Date: 26 March 2020 CODEN: RSCAC Correspondence Address: Potter, B.V.L.; Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, United Kingdom; email: barry.potter@pharm.ox.ac.uk Funding details: European Commission, EU, DLV-813284 Funding details: Deutsche Forschungsgemeinschaft, DFG, SFB1328, 335447717 Funding details: Wellcome Trust, WT Funding text 1: This work was supported by the Deutsche For-schungsgemeinscha (DFG) (Project number 335447717; SFB1328, project A01 to A. H. G, SFB1328, project A05 to R. F) and the Wellcome Trust. BVLP is a Wellcome Trust Senior Investigator (Grant 101010). Research in the Guse/Fliegert labs is also supported by the Joachim-Herz-Foundation, Infecto-physics consortium, project 4; and EU project INTEGRATA - DLV-813284. Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, United Kingdom Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, United Kingdom Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center, Hamburg-Eppendorf Martinistrasse 52, Hamburg, 20246, Germany Export Date: 3 July 2020 CODEN: RSCAC Correspondence Address: Potter, B.V.L.; Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, United Kingdom; email: barry.potter@pharm.ox.ac.uk Funding details: European Commission, EU, DLV-813284 Funding details: Deutsche Forschungsgemeinschaft, DFG, SFB1328, 335447717 Funding details: Wellcome Trust, WT Funding text 1: This work was supported by the Deutsche For-schungsgemeinscha (DFG) (Project number 335447717; SFB1328, project A01 to A. H. G, SFB1328, project A05 to R. F) and the Wellcome Trust. BVLP is a Wellcome Trust Senior Investigator (Grant 101010). Research in the Guse/Fliegert labs is also supported by the Joachim-Herz-Foundation, Infecto-physics consortium, project 4; and EU project INTEGRATA - DLV-813284. Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, United Kingdom Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, United Kingdom Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center, Hamburg-Eppendorf Martinistrasse 52, Hamburg, 20246, Germany Export Date: 14 July 2020 CODEN: RSCAC Correspondence Address: Potter, B.V.L.; Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, United Kingdom; email: barry.potter@pharm.ox.ac.uk Funding details: European Commission, EU, DLV-813284 Funding details: Deutsche Forschungsgemeinschaft, DFG, SFB1328, 335447717 Funding details: Wellcome Trust, WT Funding text 1: This work was supported by the Deutsche For-schungsgemeinscha (DFG) (Project number 335447717; SFB1328, project A01 to A. H. G, SFB1328, project A05 to R. F) and the Wellcome Trust. BVLP is a Wellcome Trust Senior Investigator (Grant 101010). Research in the Guse/Fliegert labs is also supported by the Joachim-Herz-Foundation, Infecto-physics consortium, project 4; and EU project INTEGRATA - DLV-813284. Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, United Kingdom Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, United Kingdom Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center, Hamburg-Eppendorf Martinistrasse 52, Hamburg, 20246, Germany Cited By :3 Export Date: 9 December 2020 CODEN: RSCAC Correspondence Address: Potter, B.V.L.; Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, United Kingdom; email: barry.potter@pharm.ox.ac.uk Funding details: European Commission, EU, DLV-813284 Funding details: Deutsche Forschungsgemeinschaft, DFG, SFB1328, 335447717 Funding details: Wellcome Trust, WT Funding text 1: This work was supported by the Deutsche For-schungsgemeinscha (DFG) (Project number 335447717; SFB1328, project A01 to A. H. G, SFB1328, project A05 to R. F) and the Wellcome Trust. BVLP is a Wellcome Trust Senior Investigator (Grant 101010). Research in the Guse/Fliegert labs is also supported by the Joachim-Herz-Foundation, Infecto-physics consortium, project 4; and EU project INTEGRATA - DLV-813284. Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, United Kingdom Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, United Kingdom Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center, Hamburg-Eppendorf Martinistrasse 52, Hamburg, 20246, Germany Cited By :3 Export Date: 9 April 2021 CODEN: RSCAC Correspondence Address: Potter, B.V.L.; Medicinal Chemistry and Drug Discovery, Mansfield Road, United Kingdom; email: barry.potter@pharm.ox.ac.uk Funding details: Wellcome Trust, WT Funding details: European Commission, EU, DLV-813284 Funding details: Deutsche Forschungsgemeinschaft, DFG, 335447717, SFB1328 Funding text 1: This work was supported by the Deutsche For-schungsgemeinscha (DFG) (Project number 335447717; SFB1328, project A01 to A. H. G, SFB1328, project A05 to R. F) and the Wellcome Trust. BVLP is a Wellcome Trust Senior Investigator (Grant 101010). Research in the Guse/Fliegert labs is also supported by the Joachim-Herz-Foundation, Infecto-physics consortium, project 4; and EU project INTEGRATA - DLV-813284. AB - Adenosine 5′-diphosphate ribose (ADPR) is an intracellular signalling molecule generated from nicotinamide adenine dinucleotide (NAD+). Synthetic ADPR analogues can shed light on the mechanism of activation of ADPR targets and their downstream effects. Such chemical biology studies, however, are often challenging due to the negatively charged pyrophosphate that is also sensitive to cellular pyrophosphatases. Prior work on an initial ADPR target, the transient receptor potential cation channel TRPM2, showed complete pyrophosphate group replacement to be a step too far in maintaining biological activity. Thus, we designed ADPR analogues with just one of the negatively charged phosphate groups removed, by employing a phosphonoacetate linker. Synthesis of two novel phosphonoacetate ADPR analogues is described via tandem N,N′-dicyclohexylcarbodiimide coupling to phosphonoacetic acid. Neither analogue, however, showed significant agonist or antagonist activity towards TRPM2, underlining the importance of a complete pyrophosphate motif in activation of this particular receptor. © 2019 The Royal Society of Chemistry. LA - English DB - MTMT ER - TY - JOUR AU - Cruz-Torres, I. AU - Backos, D.S. AU - Herson, P.S. TI - Characterization and optimization of the novel transient receptor potential melastatin 2 antagonist TaTM2Nx JF - MOLECULAR PHARMACOLOGY J2 - MOL PHARMACOL VL - 97 PY - 2020 IS - 2 SP - 102 EP - 111 PG - 10 SN - 0026-895X DO - 10.1124/mol.119.117549 UR - https://m2.mtmt.hu/api/publication/31368948 ID - 31368948 N1 - Departments of Pharmacology, United States Anesthesiology, United States Neuronal Injury and Plasticity Program, University of Colorado School of Medicine, Aurora, CO, United States Department of Pharmaceutical Sciences, University of Colorado Skaggs, School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, United States Department of Anesthesiology, University of Colorado School of Medicine, 12800 E. 19th Ave, Aurora, CO 80045, United States Export Date: 3 July 2020 CODEN: MOPMA Correspondence Address: Cruz-Torres, I.; Department of Anesthesiology, University of Colorado School of Medicine, 12800 E. 19th Ave, United States; email: ivelisse.cruz-torres@ucdenver.edu Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; Calcium; Peptides; tat Gene Products, Human Immunodeficiency Virus; TRPM Cation Channels; TRPM2 protein, human Funding details: National Institutes of Health, NIH, T32GM007635, R01NS092645 Funding text 1: This work was supported by the National Institutes of Health Grant T32GM007635 (Pharmacology Training Grant) and Grant R01NS092645 (to P.S.H.). https://doi.org/10.1124/mol.119.117549. s This article has supplemental material available at molpharm.aspetjournals. org. Departments of Pharmacology, United States Anesthesiology, United States Neuronal Injury and Plasticity Program, University of Colorado School of Medicine, Aurora, CO, United States Department of Pharmaceutical Sciences, University of Colorado Skaggs, School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, United States Department of Anesthesiology, University of Colorado School of Medicine, 12800 E. 19th Ave, Aurora, CO 80045, United States Export Date: 14 July 2020 CODEN: MOPMA Correspondence Address: Cruz-Torres, I.; Department of Anesthesiology, University of Colorado School of Medicine, 12800 E. 19th Ave, United States; email: ivelisse.cruz-torres@ucdenver.edu Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; Calcium; Peptides; tat Gene Products, Human Immunodeficiency Virus; TRPM Cation Channels; TRPM2 protein, human Funding details: National Institutes of Health, NIH, T32GM007635, R01NS092645 Funding text 1: This work was supported by the National Institutes of Health Grant T32GM007635 (Pharmacology Training Grant) and Grant R01NS092645 (to P.S.H.). https://doi.org/10.1124/mol.119.117549. s This article has supplemental material available at molpharm.aspetjournals. org. Departments of Pharmacology, United States Anesthesiology, United States Neuronal Injury and Plasticity Program, University of Colorado School of Medicine, Aurora, CO, United States Department of Pharmaceutical Sciences, University of Colorado Skaggs, School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, United States Department of Anesthesiology, University of Colorado School of Medicine, 12800 E. 19th Ave, Aurora, CO 80045, United States Cited By :1 Export Date: 9 December 2020 CODEN: MOPMA Correspondence Address: Cruz-Torres, I.; Department of Anesthesiology, University of Colorado School of Medicine, 12800 E. 19th Ave, United States; email: ivelisse.cruz-torres@ucdenver.edu Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; Calcium; Peptides; tat Gene Products, Human Immunodeficiency Virus; TRPM Cation Channels; TRPM2 protein, human Funding details: National Institutes of Health, NIH, T32GM007635, R01NS092645 Funding text 1: This work was supported by the National Institutes of Health Grant T32GM007635 (Pharmacology Training Grant) and Grant R01NS092645 (to P.S.H.). https://doi.org/10.1124/mol.119.117549. s This article has supplemental material available at molpharm.aspetjournals. org. AB - Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable channel activated by adenosine diphosphate ribose metabolites and oxidative stress. TRPM2 contributes to neuronal injury in the brain caused by stroke and cardiac arrest among other diseases including pain, inflammation, and cancer. However, the lack of specific inhibitors hinders the study of TRPM2 in brain pathophysiology. Here, we present the design of a novel TRPM2 antagonist, tatM2NX, which prevents ligand binding and TRPM2 activation. We used mutagenesis of tatM2NX to determine the structure-activity relationship and antagonistic mechanism on TRPM2 using whole-cell patch clamp and Calcium imaging in human embryonic kidney 293 cells with stable human TRPM2 expression. We show that tatM2NX inhibits over 90% of TRPM2 channel currents at concentrations as low as 2 mM. Moreover, tatM2NX is a potent antagonist with an IC50 of 396 nM. Our results from tatM2NX mutagenesis indicate that specific residues within the tatM2NX C terminus are required to confer antagonism on TRPM2. Therefore, the peptide tatM2NX represents a new tool for the study of TRPM2 function in cell biology and enhances our understanding of TRPM2 in disease. SIGNIFICANCE STATEMENT TatM2NX is a potent TRPM2 channel antagonist with the potential for clinical benefit in neurological diseases. This study characterizes interactions of tatM2NX with TRPM2 and the mechanism of action using structure-activity analysis. © 2020 by The American Society for Pharmacology and Experimental Therapeutics LA - English DB - MTMT ER - TY - CHAP AU - Galione, A. AU - Chuang, K.-T. TI - Pyridine Nucleotide Metabolites and Calcium Release from Intracellular Stores T2 - Calcium Signaling (2nd edition) VL - 1131 PB - Springer Netherlands CY - New York, New York T3 - Advances in Experimental Medicine and Biology, ISSN 0065-2598 ; 1131. PY - 2020 SP - 371 EP - 394 PG - 24 DO - 10.1007/978-3-030-12457-1_15 UR - https://m2.mtmt.hu/api/publication/31042546 ID - 31042546 N1 - Export Date: 7 January 2020 CODEN: AEMBA Correspondence Address: Galione, A.; Department of Pharmacology, University of OxfordUnited Kingdom; email: antony.galione@pharm.ox.ac.uk Export Date: 8 January 2020 CODEN: AEMBA Correspondence Address: Galione, A.; Department of Pharmacology, University of OxfordUnited Kingdom; email: antony.galione@pharm.ox.ac.uk Cited By :1 Export Date: 3 July 2020 CODEN: AEMBA Correspondence Address: Galione, A.; Department of Pharmacology, University of OxfordUnited Kingdom; email: antony.galione@pharm.ox.ac.uk Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; nicotinic acid, 54-86-4, 59-67-6; nicotinic acid adenine dinucleotide phosphate, 5502-96-5; calcium, 7440-70-2, 14092-94-5; cyclic adenosine diphosphate ribose, 119340-53-3; nicotinamide adenine dinucleotide phosphate, 53-59-8; Calcium; Cyclic ADP-Ribose; NADP; Pyridines; Ryanodine Receptor Calcium Release Channel Cited By :1 Export Date: 9 December 2020 CODEN: AEMBA Correspondence Address: Galione, A.; Department of Pharmacology, University of OxfordUnited Kingdom; email: antony.galione@pharm.ox.ac.uk Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; nicotinic acid, 54-86-4, 59-67-6; nicotinic acid adenine dinucleotide phosphate, 5502-96-5; calcium, 7440-70-2, 14092-94-5; cyclic adenosine diphosphate ribose, 119340-53-3; nicotinamide adenine dinucleotide phosphate, 53-59-8; Calcium; Cyclic ADP-Ribose; NADP; Pyridines; Ryanodine Receptor Calcium Release Channel LA - English DB - MTMT ER - TY - JOUR AU - Huang, Yihe AU - Fliegert, Ralf AU - Guse, Andreas H. AU - Lu, Wei AU - Du, Juan TI - A structural overview of the ion channels of the TRPM family JF - CELL CALCIUM J2 - CELL CALCIUM VL - 85 PY - 2020 PG - 11 SN - 0143-4160 DO - 10.1016/j.ceca.2019.102111 UR - https://m2.mtmt.hu/api/publication/31042507 ID - 31042507 N1 - Funding Agency and Grant Number: McKnight Scholar Award; Klingenstein-Simon Scholar Award; National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R01NS111031-01]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R56HL144929-01]; Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation)German Research Foundation (DFG) [335447727 -SFB 1328, INTEGRATA -DLV-813284] Funding text: We thank D. Nadziejka for technical editing. We appreciate Du and Lu lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award, and a National Institutes of Health (NIH) grant (1R01NS111031-01). W.L. is supported by a NIH grant (1R56HL144929-01). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) -Project-ID: 335447727 -SFB 1328 (Joachim-Herz-Foundation, Infectophysics consortium, project 4; and EU project INTEGRATA -DLV-813284). Export Date: 7 January 2020 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Export Date: 8 January 2020 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Van Andel Institute, 333 Bostwick Ave., N.E., Grand Rapids, MI 49503, United States The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, D-20246, Germany Export Date: 14 February 2020 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Funding details: European Commission, EU, INTEGRATA - DLV-813284 Funding details: McKnight Foundation Funding details: National Institutes of Health, NIH, 1R56HL144929-01, 1R01NS111031-01 Funding details: German-Israeli Foundation for Scientific Research and Development, GIF, SFB 1328 Funding text 1: We thank D. Nadziejka for technical editing. We appreciate Du and Lü lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award , and a National Institutes of Health (NIH) grant ( 1R01NS111031-01 ). W.L. is supported by a NIH grant ( 1R56HL144929-01 ). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) - Project-ID: 335447727 - SFB 1328 ( Joachim-Herz-Foundation , Infectophysics consortium, project 4 ; and EU project INTEGRATA - DLV-813284 ). Van Andel Institute, 333 Bostwick Ave., N.E., Grand Rapids, MI 49503, United States The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, D-20246, Germany Cited By :6 Export Date: 1 July 2020 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Funding details: European Commission, EU, INTEGRATA - DLV-813284 Funding details: McKnight Foundation Funding details: National Institutes of Health, NIH, 1R56HL144929-01, 1R01NS111031-01 Funding details: German-Israeli Foundation for Scientific Research and Development, GIF, SFB 1328 Funding text 1: We thank D. Nadziejka for technical editing. We appreciate Du and Lü lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award , and a National Institutes of Health (NIH) grant ( 1R01NS111031-01 ). W.L. is supported by a NIH grant ( 1R56HL144929-01 ). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) - Project-ID: 335447727 - SFB 1328 ( Joachim-Herz-Foundation , Infectophysics consortium, project 4 ; and EU project INTEGRATA - DLV-813284 ). Van Andel Institute, 333 Bostwick Ave., N.E., Grand Rapids, MI 49503, United States The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, D-20246, Germany Cited By :6 Export Date: 3 July 2020 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Funding details: European Commission, EU, INTEGRATA - DLV-813284 Funding details: McKnight Foundation Funding details: National Institutes of Health, NIH, 1R56HL144929-01, 1R01NS111031-01 Funding details: German-Israeli Foundation for Scientific Research and Development, GIF, SFB 1328 Funding text 1: We thank D. Nadziejka for technical editing. We appreciate Du and Lü lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award , and a National Institutes of Health (NIH) grant ( 1R01NS111031-01 ). W.L. is supported by a NIH grant ( 1R56HL144929-01 ). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) - Project-ID: 335447727 - SFB 1328 ( Joachim-Herz-Foundation , Infectophysics consortium, project 4 ; and EU project INTEGRATA - DLV-813284 ). Van Andel Institute, 333 Bostwick Ave., N.E., Grand Rapids, MI 49503, United States The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, D-20246, Germany Cited By :6 Export Date: 14 July 2020 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Funding details: European Commission, EU, INTEGRATA - DLV-813284 Funding details: McKnight Foundation Funding details: National Institutes of Health, NIH, 1R56HL144929-01, 1R01NS111031-01 Funding details: German-Israeli Foundation for Scientific Research and Development, GIF, SFB 1328 Funding text 1: We thank D. Nadziejka for technical editing. We appreciate Du and Lü lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award , and a National Institutes of Health (NIH) grant ( 1R01NS111031-01 ). W.L. is supported by a NIH grant ( 1R56HL144929-01 ). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) - Project-ID: 335447727 - SFB 1328 ( Joachim-Herz-Foundation , Infectophysics consortium, project 4 ; and EU project INTEGRATA - DLV-813284 ). Van Andel Institute, 333 Bostwick Ave., N.E., Grand Rapids, MI 49503, United States The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, D-20246, Germany Cited By :6 Export Date: 20 July 2020 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Funding details: European Commission, EU, INTEGRATA - DLV-813284 Funding details: McKnight Foundation Funding details: National Institutes of Health, NIH, 1R56HL144929-01, 1R01NS111031-01 Funding details: German-Israeli Foundation for Scientific Research and Development, GIF, SFB 1328 Funding text 1: We thank D. Nadziejka for technical editing. We appreciate Du and Lü lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award , and a National Institutes of Health (NIH) grant ( 1R01NS111031-01 ). W.L. is supported by a NIH grant ( 1R56HL144929-01 ). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) - Project-ID: 335447727 - SFB 1328 ( Joachim-Herz-Foundation , Infectophysics consortium, project 4 ; and EU project INTEGRATA - DLV-813284 ). Van Andel Institute, 333 Bostwick Ave., N.E., Grand Rapids, MI 49503, United States The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, D-20246, Germany Cited By :18 Export Date: 9 December 2020 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Funding details: European Commission, EU, INTEGRATA - DLV-813284 Funding details: McKnight Foundation Funding details: National Institutes of Health, NIH, 1R56HL144929-01, 1R01NS111031-01 Funding details: German-Israeli Foundation for Scientific Research and Development, GIF, SFB 1328 Funding text 1: We thank D. Nadziejka for technical editing. We appreciate Du and Lü lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award , and a National Institutes of Health (NIH) grant ( 1R01NS111031-01 ). W.L. is supported by a NIH grant ( 1R56HL144929-01 ). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) - Project-ID: 335447727 - SFB 1328 ( Joachim-Herz-Foundation , Infectophysics consortium, project 4 ; and EU project INTEGRATA - DLV-813284 ). Van Andel Institute, 333 Bostwick Ave., N.E., Grand Rapids, MI 49503, United States The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, D-20246, Germany Cited By :27 Export Date: 9 April 2021 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Funding details: National Institutes of Health, NIH, 1R01NS111031-01, 1R56HL144929-01 Funding details: McKnight Foundation Funding details: European Commission, EU, INTEGRATA - DLV-813284 Funding details: Deutsche Forschungsgemeinschaft, DFG, 335447727 - SFB 1328 Funding details: German-Israeli Foundation for Scientific Research and Development, GIF, SFB 1328 Funding text 1: We thank D. Nadziejka for technical editing. We appreciate Du and Lü lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award , and a National Institutes of Health (NIH) grant ( 1R01NS111031-01 ). W.L. is supported by a NIH grant ( 1R56HL144929-01 ). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) - Project-ID: 335447727 - SFB 1328 ( Joachim-Herz-Foundation , Infectophysics consortium, project 4 ; and EU project INTEGRATA - DLV-813284 ). Funding text 2: We thank D. Nadziejka for technical editing. We appreciate Du and L? lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award, and a National Institutes of Health (NIH) grant (1R01NS111031-01). W.L. is supported by a NIH grant (1R56HL144929-01). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) - Project-ID: 335447727 - SFB 1328 (Joachim-Herz-Foundation, Infectophysics consortium, project 4; and EU project INTEGRATA - DLV-813284). AB - The TRPM (transient receptor potential melastatin) family belongs to the superfamily of TRP cation channels. The TRPM subfamily is composed of eight members that are involved in diverse biological functions such as temperature sensing, inflammation, insulin secretion, and redox sensing. Since the first cloning of TRPM1 in 1998, tremendous progress has been made uncovering the function, structure, and pharmacology of this family. Complete structures of TRPM2, TRPM4, and TRPM8, as well as a partial structure of TRPM7, have been determined by cryo-EM, providing insights into their channel assembly, ion permeation, gating mechanisms, and structural pharmacology. Here we summarize the current knowledge about channel structure, emphasizing general features and principles of the structure of TRPM channels discovered since 2017. We also discuss some of the key unresolved issues in the field, including the molecular mechanisms underlying voltage and temperature dependence, as well as the functions of the TRPM channels' C-terminal domains. LA - English DB - MTMT ER - TY - JOUR AU - Kuehn, Frank J. P. TI - Structure-Function Relationship of TRPM2: Recent Advances, Contradictions, and Open Questions JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 21 PY - 2020 IS - 18 PG - 16 SN - 1661-6596 DO - 10.3390/ijms21186481 UR - https://m2.mtmt.hu/api/publication/31697231 ID - 31697231 N1 - Export Date: 9 December 2020 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, University Hospital RWTH AachenGermany; email: fkuehn@ukaachen.de Funding details: Deutsche Forschungsgemeinschaft, DFG, KU 2271/4-2 Funding text 1: Funding: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). Export Date: 7 April 2021 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Germany; email: fkuehn@ukaachen.de Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; Calcium; TRPM Cation Channels; TRPM2 protein, human Funding details: Deutsche Forschungsgemeinschaft, DFG, KU 2271/4-2 Funding text 1: Funding: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). Export Date: 9 April 2021 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Germany; email: fkuehn@ukaachen.de Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; Calcium; TRPM Cation Channels; TRPM2 protein, human Funding details: Deutsche Forschungsgemeinschaft, DFG, KU 2271/4-2 Funding text 1: Funding: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). Export Date: 12 April 2021 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Germany; email: fkuehn@ukaachen.de Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; Calcium; TRPM Cation Channels; TRPM2 protein, human Funding details: Deutsche Forschungsgemeinschaft, DFG, KU 2271/4-2 Funding text 1: Funding: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). Cited By :5 Export Date: 9 September 2021 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Germany; email: fkuehn@ukaachen.de Chemicals/CAS: adenosine triphosphate, 15237-44-2, 56-65-5, 987-65-5; hemagglutinin, 37333-12-3; serine, 56-45-1, 6898-95-9; calcium, 7440-70-2, 14092-94-5; Calcium; TRPM Cation Channels; TRPM2 protein, human Funding details: Deutsche Forschungsgemeinschaft, DFG, KU 2271/4-2 Funding text 1: Funding: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). Cited By :5 Export Date: 15 September 2021 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Germany; email: fkuehn@ukaachen.de Chemicals/CAS: adenosine triphosphate, 15237-44-2, 56-65-5, 987-65-5; hemagglutinin, 37333-12-3; serine, 56-45-1, 6898-95-9; calcium, 7440-70-2, 14092-94-5; Calcium; TRPM Cation Channels; TRPM2 protein, human Funding details: Deutsche Forschungsgemeinschaft, DFG, KU 2271/4-2 Funding text 1: Funding: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). AB - When in a particular scientific field, major progress is rapidly reached after a long period of relative stand-still, this is often achieved by the development or exploitation of new techniques and methods. A striking example is the new insights brought into the understanding of the gating mechanism of the transient receptor potential melastatin type 2 cation channel (TRPM2) by cryogenic electron microscopy structure analysis. When conventional methods are complemented by new ones, it is quite natural that established researchers are not fully familiar with the possibilities and limitations of the new method. On the other hand, newcomers may need some assistance in perceiving the previous knowledge in detail; they may not realize that some of their interpretations are at odds with previous results and need refinement. This may in turn trigger further studies with new and promising perspectives, combining the promises of several methodological approaches. With this review, I aim to give a comprehensive overview on functional data of several orthologous of TRPM2 that are nicely explained by structural studies. Moreover, I wish to point out some functional contradictions raised by the structural data. Finally, some open questions and some lines of possible future experimental approaches shall be discussed. LA - English DB - MTMT ER - TY - JOUR AU - Lu, Wei AU - Du, Juan TI - The N-terminal domain in TRPM2 channel is a conserved nucleotide binding site JF - JOURNAL OF GENERAL PHYSIOLOGY J2 - J GEN PHYSIOL VL - 152 PY - 2020 IS - 5 SN - 0022-1295 DO - 10.1085/jgp.201912555 UR - https://m2.mtmt.hu/api/publication/31366156 ID - 31366156 LA - English DB - MTMT ER - TY - JOUR AU - Malko, P. AU - Jiang, L.-H. TI - TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions JF - REDOX BIOLOGY J2 - REDOX BIOL VL - 37 PY - 2020 PG - 20 SN - 2213-2317 DO - 10.1016/j.redox.2020.101755 UR - https://m2.mtmt.hu/api/publication/31731758 ID - 31731758 N1 - Cited By :25 Export Date: 12 December 2022 Correspondence Address: Jiang, L.-H.; School of Biomedical Science, United Kingdom; email: l.h.jiang@leeds.ac.uk AB - Oxidative stress resulting from the accumulation of high levels of reactive oxygen species is a salient feature of, and a well-recognised pathological factor for, diverse pathologies. One common mechanism for oxidative stress damage is via the disruption of intracellular ion homeostasis to induce cell death. TRPM2 is a non-selective Ca2+-permeable cation channel with a wide distribution throughout the body and is highly sensitive to activation by oxidative stress. Recent studies have collected abundant evidence to show its important role in mediating cell death induced by miscellaneous oxidative stress-inducing pathological factors, both endogenous and exogenous, including ischemia/reperfusion and the neurotoxicants amyloid-β peptides and MPTP/MPP+ that cause neuronal demise in the brain, myocardial ischemia/reperfusion, proinflammatory mediators that disrupt endothelial function, diabetogenic agent streptozotocin and diabetes risk factor free fatty acids that induce loss of pancreatic β-cells, bile acids that damage pancreatic acinar cells, renal ischemia/reperfusion and albuminuria that are detrimental to kidney cells, acetaminophen that triggers hepatocyte death, and nanoparticles that injure pericytes. Studies have also shed light on the signalling mechanisms by which these pathological factors activate the TRPM2 channel to alter intracellular ion homeostasis leading to aberrant initiation of various cell death pathways. TRPM2-mediated cell death thus emerges as an important mechanism in the pathogenesis of conditions including ischemic stroke, neurodegenerative diseases, cardiovascular diseases, diabetes, pancreatitis, chronic kidney disease, liver damage and neurovascular injury. These findings raise the exciting perspective of targeting the TRPM2 channel as a novel therapeutic strategy to treat such oxidative stress-associated diseases. © 2020 The Author(s) LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Balázs AU - Iordanov, Iordan AU - Csanády, László TI - Selective profiling of N- And C-terminal nucleotide-binding sites in a TRPM2 channel JF - JOURNAL OF GENERAL PHYSIOLOGY J2 - J GEN PHYSIOL VL - 152 PY - 2020 IS - 5 PG - 13 SN - 0022-1295 DO - 10.1085/jgp.201912533 UR - https://m2.mtmt.hu/api/publication/31365406 ID - 31365406 N1 - Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary MTA-SE Lendület Ion Channel Research Group, Semmelweis University, Budapest, Hungary Cited By :7 Export Date: 15 September 2021 CODEN: JGPLA Correspondence Address: Tóth, B.; Department of Medical Biochemistry, Hungary; email: toth.balazs@med.semmelweis-univ.hu Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; amino acid, 65072-01-7; calcium, 7440-70-2, 14092-94-5; Adenosine Diphosphate Ribose; Amino Acids; Calcium; Ligands; Nucleotides; TRPM Cation Channels; TRPM2 protein, human Funding details: Semmelweis Egyetem, 18-4-SE-132, 19-4-SE-49 Funding details: Magyar Tudományos Akadémia, MTA, LP2017-14/2017 Funding text 1: Supported by the Hungarian Academy of Sciences (Lendület grant LP2017-14/2017 to L. Csanády) and a Ministry of Human Capacities of Hungary New National Excellence Program (Új Nemzeti Kiválóság Program) award to Semmelweis University. B. Tóth is a János Bolyai Research Fellow, supported by postdoctoral Új Nemzeti Kiválóság Program grants 18-4-SE-132 and 19-4-SE-49. The authors declare no competing financial interests. AB - Transient receptor potential melastatin 2 (TRPM2) is a homotetrameric Ca2+-permeable cation channel important for the immune response, body temperature regulation, and insulin secretion, and is activated by cytosolic Ca2+ and ADP ribose (ADPR). ADPR binds to two distinct locations, formed by large N- and C-terminal cytosolic domains, respectively, of the channel protein. In invertebrate TRPM2 channels, the C-terminal site is not required for channel activity but acts as an active ADPR phosphohydrolase that cleaves the activating ligand. In vertebrate TRPM2 channels, the C-terminal site is catalytically inactive but cooperates with the N-terminal site in channel activation. The precise functional contributions to channel gating and the nucleotide selectivities of the two sites in various species have not yet been deciphered. For TRPM2 of the sea anemone Nematostella vectensis (nvTRPM2), catalytic activity is solely attributable to the C-terminal site. Here, we show that nvTRPM2 channel gating properties remain unaltered upon deletion of the C-terminal domain, indicating that the N-terminal site is single-handedly responsible for channel gating. Exploiting such functional independence of the N- and C-terminal sites, we selectively measure their affinity profiles for a series of ADPR analogues, as reflected by apparent affinities for channel activation and catalysis, respectively. Using site-directed mutagenesis, we confirm that the same N-terminal site observed in vertebrate TRPM2 channels was already present in ancient cnidarians. Finally, by characterizing the functional effects of six amino acid side chain truncations in the N-terminal site, we provide first insights into the mechanistic contributions of those side chains to TRPM2 channel gating. © 2020 Tóth et al. This article is distributed under the terms of an Attribution-Noncommercial-Share Alike-No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). LA - English DB - MTMT ER - TY - JOUR AU - Wang, L. AU - Negro, R. AU - Wu, H. TI - TRPM2, linking oxidative stress and Ca2+ permeation to NLRP3 inflammasome activation JF - CURRENT OPINION IN IMMUNOLOGY J2 - CURR OPIN IMMUNOL VL - 62 PY - 2020 SP - 131 EP - 135 PG - 5 SN - 0952-7915 DO - 10.1016/j.coi.2020.01.005 UR - https://m2.mtmt.hu/api/publication/31366809 ID - 31366809 N1 - Export Date: 1 July 2020 CODEN: COPIE Chemicals/CAS: calcium ion, 14127-61-8; interleukin 1beta converting enzyme, 122191-40-6, 187414-12-6 Export Date: 3 July 2020 CODEN: COPIE Chemicals/CAS: calcium ion, 14127-61-8; interleukin 1beta converting enzyme, 122191-40-6, 187414-12-6 AB - The NLRP3 inflammasome is an innate immune platform that senses various pathogens and sterile insults. NLRP3 stimulation leads to activation of caspase-1, the secretion of pro-inflammatory cytokines and an inflammatory cell death called pyroptosis. Effectors of the NLRP3 inflammasome efficiently drive an immune response, not only providing protection in physiological settings but also promoting pathology when over activated. Generation of reactive oxygen species (ROS) and intracellular calcium mobilization can activate the NLRP3 inflammasome. Recent studies suggest that TRPM2 is a calcium-permeable cation channel mediating ROS-dependent NLRP3 activation. Here, we review the role of TRPM2 in NLRP3 inflammasome activation and provide an update on new functional and structural discoveries. Understanding the molecular mechanism of TRPM2 dependent NLRP3 inflammasome activation will shed lights on this complex pathway and help the developing of therapeutic strategies. © 2020 Elsevier Ltd LA - English DB - MTMT ER - TY - JOUR AU - Yu, Peilin AU - Cai, Xiaobo AU - Liang, Yan AU - Wang, Mingxiang AU - Yang, Wei TI - Roles of NAD+ and its metabolites regulated calcium channels in cancer JF - MOLECULES J2 - MOLECULES VL - 25 PY - 2020 IS - 20 PG - 20 SN - 1420-3049 DO - 10.3390/molecules25204826 UR - https://m2.mtmt.hu/api/publication/31647884 ID - 31647884 N1 - Department of Toxicology, Department of Medical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China Department of Biophysics, Department of Neurosurgery of the, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China BrioPryme Biologics, Inc., Hangzhou, Zhejiang 310058, China CODEN: MOLEF Correspondence Address: Yang, W.; Department of Biophysics, Department of Neurosurgery of the, First Affiliated Hospital, Zhejiang University School of MedicineChina; email: yangwei@zju.edu.cn Funding details: Natural Science Foundation of Zhejiang Province, LY19B020013 Funding details: National Natural Science Foundation of China, NSFC, 31872796, 32071102, 81371302 Funding text 1: Funding: This work was supported by the Natural Science Foundation of China (31872796 and 81371302 to W.Y., 32071102 to P.Y.), and Zhejiang Provincial Natural Science Foundation (LY19B020013 to P.Y.). Department of Toxicology, Department of Medical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China Department of Biophysics, Department of Neurosurgery of the, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China BrioPryme Biologics, Inc., Hangzhou, Zhejiang 310058, China Export Date: 8 December 2020 CODEN: MOLEF Correspondence Address: Yang, W.; Department of Biophysics, Department of Neurosurgery of the, First Affiliated Hospital, Zhejiang University School of MedicineChina; email: yangwei@zju.edu.cn Funding details: Natural Science Foundation of Zhejiang Province, LY19B020013 Funding details: National Natural Science Foundation of China, NSFC, 31872796, 32071102, 81371302 Funding text 1: Funding: This work was supported by the Natural Science Foundation of China (31872796 and 81371302 to W.Y., 32071102 to P.Y.), and Zhejiang Provincial Natural Science Foundation (LY19B020013 to P.Y.). Department of Toxicology, Department of Medical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China Department of Biophysics, Department of Neurosurgery of the, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China BrioPryme Biologics, Inc., Hangzhou, Zhejiang 310058, China Export Date: 9 April 2021 CODEN: MOLEF Correspondence Address: Yang, W.; Department of Biophysics, China; email: yangwei@zju.edu.cn Funding details: National Natural Science Foundation of China, NSFC, 31872796, 32071102, 81371302 Funding details: Natural Science Foundation of Zhejiang Province, LY19B020013 Funding text 1: Funding: This work was supported by the Natural Science Foundation of China (31872796 and 81371302 to W.Y., 32071102 to P.Y.), and Zhejiang Provincial Natural Science Foundation (LY19B020013 to P.Y.). Department of Toxicology, Department of Medical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China Department of Biophysics, Department of Neurosurgery of the, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China BrioPryme Biologics, Inc., Hangzhou, Zhejiang 310058, China Export Date: 12 April 2021 CODEN: MOLEF Correspondence Address: Yang, W.; Department of Biophysics, China; email: yangwei@zju.edu.cn Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; nicotinamide adenine dinucleotide, 53-84-9; Calcium; Calcium Channels; MCOLN1 protein, human; NAD; Transient Receptor Potential Channels; TRPM Cation Channels; TRPM2 protein, human Funding details: National Natural Science Foundation of China, NSFC, 31872796, 32071102, 81371302 Funding details: Natural Science Foundation of Zhejiang Province, LY19B020013 Funding text 1: Funding: This work was supported by the Natural Science Foundation of China (31872796 and 81371302 to W.Y., 32071102 to P.Y.), and Zhejiang Provincial Natural Science Foundation (LY19B020013 to P.Y.). Department of Toxicology, Department of Medical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China Department of Biophysics, Department of Neurosurgery of the, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China BrioPryme Biologics, Inc., Hangzhou, Zhejiang 310058, China Cited By :1 Export Date: 9 September 2021 CODEN: MOLEF Correspondence Address: Yang, W.; Department of Biophysics, China; email: yangwei@zju.edu.cn Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; nicotinamide adenine dinucleotide, 53-84-9; Calcium; Calcium Channels; MCOLN1 protein, human; NAD; Transient Receptor Potential Channels; TRPM Cation Channels; TRPM2 protein, human Funding details: National Natural Science Foundation of China, NSFC, 31872796, 32071102, 81371302 Funding details: Natural Science Foundation of Zhejiang Province, LY19B020013 Funding text 1: Funding: This work was supported by the Natural Science Foundation of China (31872796 and 81371302 to W.Y., 32071102 to P.Y.), and Zhejiang Provincial Natural Science Foundation (LY19B020013 to P.Y.). AB - Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor for redox enzymes, but also moonlights as a regulator for ion channels, the same as its metabolites. Ca2+ homeostasis is dysregulated in cancer cells and affects processes such as tumorigenesis, angiogenesis, autophagy, progression, and metastasis. Herein, we summarize the regulation of the most common calcium channels (TRPM2, TPCs, RyRs, and TRPML1) by NAD+ and its metabolites, with a particular focus on their roles in cancers. Although the mechanisms of NAD+ metabolites in these pathological processes are yet to be clearly elucidated, these ion channels are emerging as potential candidates of alternative targets for anticancer therapy. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. LA - English DB - MTMT ER - TY - JOUR AU - Baszczyňski, Ondrej AU - Watt, Joanna M AU - Rozewitz, Monika D AU - Guse, Andreas H AU - Fliegert, Ralf AU - Potter, Barry V L TI - Synthesis of terminal ribose analogues of adenosine 5'-diphosphate ribose (ADPR) as probes for the Transient Receptor Potential (TRP) cation channel TRPM2. JF - JOURNAL OF ORGANIC CHEMISTRY J2 - J ORG CHEM VL - 84 PY - 2019 IS - 10 SP - 6143 EP - 6157 PG - 15 SN - 0022-3263 DO - 10.1021/acs.joc.9b00338 UR - https://m2.mtmt.hu/api/publication/30658837 ID - 30658837 N1 - Funding Agency and Grant Number: Wellcome TrustWellcome Trust [101010]; Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [GU 360/16-1, 335447717-SFB1328]; Landesforschungsforderung Hamburg (Research Group ReAd Me) [01] Funding text: B.V.L.P. is a Wellcome Trust Senior Investigator (grant 101010). This study was supported by the Deutsche Forschungsgemeinschaft (GU 360/16-1 and Projektnummer 335447717-SFB1328 project A01 to A.H.G., Projektnummer 335447717-SFB1328 project A05 to R.F.) and Landesforschungsforderung Hamburg (Research Group ReAd Me, project 01, to A.H.G.). The authors thank Andreas Bauche for technical support. Export Date: 7 January 2020 CODEN: JOCEA Correspondence Address: Potter, B.V.L.; Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, United Kingdom; email: barry.potter@pharm.ox.ac.uk Export Date: 8 January 2020 CODEN: JOCEA Correspondence Address: Potter, B.V.L.; Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, United Kingdom; email: barry.potter@pharm.ox.ac.uk AB - TRPM2 (transient receptor potential cation channel, subfamily M, member 2) is a non-selective cation channel involved in the response to oxidative stress and in inflammation. Its role in autoimmune and neurodegenerative diseases makes it an attractive pharmacological target. Binding of the nucleotide adenosine 5'-diphosphate ribose (ADPR) to the cytosolic NUDT9 homology (NUDT9H) domain activates the channel. A detailed understanding of how ADPR interacts with the TRPM2 ligand binding domain is lacking, hampering the rational design of modulators, but the terminal ribose of ADPR is known to be essential for activation. To study its role in more detail we designed synthetic routes to novel analogues of ADPR and 2'-deoxy-ADPR that were modified only by removal of a single hydroxyl group from of the terminal ribose. The ADPR analogues were obtained by coupling nucleoside phosphorimidazolides to deoxysugar phosphates. The corresponding C2″-based analogues proved to be unstable. The C1″- and C3″-ADPR analogues were evaluated electrophysiologically by patch-clamp in TRPM2-expressing HEK293 cells. In addition, a compound with all hydroxyl groups of the terminal ribose blocked as its 1"-α-methylfuranoside-2", 3"-isopropylidene derivative was evaluated. Removal of either C1" or C3" hydroxyl groups from ADPR resulted in loss of agonist activity. Both these modifications, and blocking all three hydroxyl groups resulted in ADPR antagonists. Our results demonstrate the critical role of these hydroxyl groups in channel activation. LA - English DB - MTMT ER - TY - JOUR AU - Hilton, Jacob K. AU - Kim, Minjoo AU - Van Horn, Wade D. TI - Structural and Evolutionary Insights Point to Allosteric Regulation of TRP Ion Channels JF - ACCOUNTS OF CHEMICAL RESEARCH J2 - ACCOUNTS CHEM RES VL - 52 PY - 2019 IS - 6 SP - 1643 EP - 1652 PG - 10 SN - 0001-4842 DO - 10.1021/acs.accounts.9b00075 UR - https://m2.mtmt.hu/api/publication/30749323 ID - 30749323 N1 - Funding Agency and Grant Number: National Institutes of General Medical SciencesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM112077] Funding text: This work was supported by the National Institutes of General Medical Sciences R01GM112077 to W.D.V.H. Export Date: 8 January 2020 CODEN: ACHRE Correspondence Address: Van Horn, W.D.; School of Molecular Sciences, Arizona State UniversityUnited States; email: wade.van.horn@asu.edu AB - The familiar pungent taste of spicy food, the refreshing taste of mint, and many other physiological phenomena are mediated by transient receptor potential (TRP) ion channels. TRP channels are a superfamily of ion channels that are sensitive to diverse chemical and physical stimuli and play diverse roles in biology. In addition to chemical regulation, some family members also sense common physical stimuli, such as temperature or pressure. Since their discovery and cloning in the 1990s and 2000s, understanding the molecular mechanisms governing TRP channel function and polymodal regulation has been a consistent but challenging goal. Until recently, a general lack of high-resolution TRP channel structures had significantly limited a molecular understanding of their function.In the past few years, a flood of TRP channel structures have been released, made possible primarily by advances in cryo-electron microscopy (cryo-EM). The boon of many structures has unleashed unparalleled insight into TRP channel architecture. Substantive comparative studies between TRP structures provide snapshots of distinct states such as ligand-free, stabilized by chemical agonists, or antagonists, partially illuminating how a given channel opens and closes. However, the now similar to 75 TRP channel structures have ushered in surprising outcomes, including a lack of an apparent general mechanism underlying channel opening and closing among family members. Similarly, the structures reveal a surprising diversity in which chemical ligands bind TRP channels.Several TRP channels are activated by temperature changes in addition to ligand binding. Unraveling mechanisms of thermosensation has proven an elusive challenge to the field. Although some studies point to thermosensitive domains in the transmembrane region of the channels, results have sometimes been contradictory and difficult to interpret; in some cases, a domain that proves essential for thermal sensitivity in one context can be entirely removed from the channel without affecting thermosensation in another context. These results are not amenable to simple interpretations and point to allosteric networks of regulation within the channel structure.TRP channels have evolved to be fine-tuned for the needs of a species in its environmental niche, a fact that has been both a benefit and burden in unlocking their molecular features. Functional evolutionary divergence has presented challenges for studying TRP channels, as orthologs from different species can give conflicting experimental results. However, this diversity can also be examined comparatively to decipher the basis for functional differences. As with structural biology, untangling the similarities and differences resulting from evolutionary pressure between species has been a rich source of data guiding the field. This Account will contextualize the existing biochemical and functional data with an eye to evolutionary data and couple these insights with emerging structural biology to better understand the molecular mechanisms behind chemical and physical regulation of TRP channels. LA - English DB - MTMT ER - TY - JOUR AU - Huang, Yihe AU - Roth, Becca AU - Lu, Wei AU - Du, Juan TI - Ligand recognition and gating mechanism through three ligand-binding sites of human TRPM2 channel JF - ELIFE J2 - ELIFE VL - 8 PY - 2019 PG - 18 SN - 2050-084X DO - 10.7554/eLife.50175 UR - https://m2.mtmt.hu/api/publication/30870275 ID - 30870275 N1 - Funding Agency and Grant Number: Esther A. and Joseph Klingenstein Fund; McKnight Endowment Fund for Neuroscience; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01NS111031] Funding text: Esther A. and Joseph Klingenstein Fund 2019 class Juan Du; McKnight Endowment Fund for Neuroscience 2019 class Juan Du; National Institutes of Health R01NS111031 Juan Du; The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Export Date: 7 January 2020 Correspondence Address: Lü, W.; Van Andel InstituteUnited States; email: wei.lu@vai.org Export Date: 8 January 2020 Correspondence Address: Lü, W.; Van Andel InstituteUnited States; email: wei.lu@vai.org AB - TRPM2 is critically involved in diverse physiological processes including core temperature sensing, apoptosis, and immune response. TRPM2's activation by Ca2+ and ADP ribose (ADPR), an NAD(+)-metabolite produced under oxidative stress and neurodegenerative conditions, suggests a role in neurological disorders. We provide a central concept between triple-site ligand binding and the channel gating of human TRPM2. We show consecutive structural rearrangements and channel activation of TRPM2 induced by binding of ADPR in two indispensable locations, and the binding of Ca2+ in the transmembrane domain. The 8-Br-cADPR-an antagonist of cADPR-binds only to the MHR1/2 domain and inhibits TRPM2 by stabilizing the channel in an apo-like conformation. We conclude that MHR1/2 acts as a orthostatic ligand-binding site for TRPM2. The NUDT9-H domain binds to a second ADPR to assist channel activation in vertebrates, but not necessary in invertebrates. Our work provides insights into the gating mechanism of human TRPM2 and its pharmacology. LA - English DB - MTMT ER - TY - JOUR AU - Iordanov, Iordan AU - Tóth, Balázs AU - Szöllősi, András AU - Csanády, László TI - Enzyme activity and selectivity filter stability of ancient TRPM2 channels were simultaneously lost in early vertebrates JF - ELIFE J2 - ELIFE VL - 8 PY - 2019 IS - 2019 PG - 23 SN - 2050-084X DO - 10.7554/eLife.44556 UR - https://m2.mtmt.hu/api/publication/30637149 ID - 30637149 N1 - Funding Agency and Grant Number: Howard Hughes Medical InstituteHoward Hughes Medical Institute; Magyar Tudomanyos Akademia [LP2017-14/2017]; Ministry of Human Capacities of Hungary [UNKP 17-4-I-SE-61, UNKP 18-4-SE-132]; Magyar Tudomanyos Akademia Funding text: Howard Hughes Medical Institute International Early Career Scientist Award Laszlo Csanady; Magyar Tudomanyos Akademia LP2017-14/2017 Laszlo Csanady; Ministry of Human Capacities of Hungary UNKP 17-4-I-SE-61 Balazs Toth; Magyar Tudomanyos Akademia Bolyai Research Fellowship Balazs Toth; Ministry of Human Capacities of Hungary UNKP-FIKP Laszlo Csanady; Ministry of Human Capacities of Hungary UNKP 18-4-SE-132 Balazs Toth; The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Export Date: 7 January 2020 Correspondence Address: Csanády, L.; Department of Medical Biochemistry, Semmelweis UniversityHungary; email: csanady.laszlo@med.semmelweis-univ.hu Export Date: 8 January 2020 Correspondence Address: Csanády, L.; Department of Medical Biochemistry, Semmelweis UniversityHungary; email: csanady.laszlo@med.semmelweis-univ.hu AB - Transient Receptor Potential Melastatin 2 (TRPM2) is a cation channel important for the immune response, insulin secretion, and body temperature regulation. It is activated by cytosolic ADP ribose (ADPR) and contains a nudix-type motif 9 (NUDT9)-homology (NUDT9-H) domain homologous to ADPR phosphohydrolases (ADPRases). Human TRPM2 (hsTRPM2) is catalytically inactive due to mutations in the conserved Nudix box sequence. Here, we show that TRPM2 Nudix motifs are canonical in all invertebrates but vestigial in vertebrates. Correspondingly, TRPM2 of the cnidarian Nematostella vectensis (nvTRPM2) and the choanoflagellate Salpingoeca rosetta (srTRPM2) are active ADPRases. Disruption of ADPRase activity fails to affect nvTRPM2 channel currents, reporting a catalytic cycle uncoupled from gating. Furthermore, pore sequence substitutions responsible for inactivation of hsTRPM2 also appeared in vertebrates. Correspondingly, zebrafish (Danio rerio) TRPM2 (drTRPM2) and hsTRPM2 channels inactivate, but srTRPM2 and nvTRPM2 currents are stable. Thus, catalysis and pore stability were lost simultaneously in vertebrate TRPM2 channels. LA - English DB - MTMT ER - TY - JOUR AU - Kuehn, Frank J. P. AU - Ehrlich, Wiebke AU - Barth, Daniel AU - Kuehn, Cornelia AU - Lueckhoff, Andreas TI - Functional importance of NUDT9H domain and N-terminal ADPR-binding pocket in two species variants of vertebrate TRPM2 channels JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 9 PY - 2019 PG - 13 SN - 2045-2322 DO - 10.1038/s41598-019-55232-5 UR - https://m2.mtmt.hu/api/publication/31042589 ID - 31042589 N1 - Funding Agency and Grant Number: Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [KU 2271/4-2] Funding text: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). We are grateful to Dr. Barry Potter and Dr. Joanna Watt from the Department of Pharmacology, University of Oxford for the generous gift of the ADPR analogues. We thank Marina Wolf for expert technical assistance. Export Date: 8 January 2020 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Medical Faculty, RWTH AachenGermany; email: fkuehn@ukaachen.de Cited By :1 Export Date: 1 July 2020 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Medical Faculty, RWTH AachenGermany; email: fkuehn@ukaachen.de Funding details: Deutsche Forschungsgemeinschaft, DFG, KU 2271/4-2 Funding text 1: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). We are grateful to Dr. Barry Potter and Dr. Joanna Watt from the Department of Pharmacology, University of Oxford for the generous gift of the ADPR analogues. We thank Marina Wolf for expert technical assistance. AB - There are at least two different principles of how ADP-ribose (ADPR) induces activation of TRPM2 channels. In human TRPM2, gating requires the C-terminal NUDT9H domain as ADPR-binding module, whereas in sea anemone, NUDT9H is dispensable and binding of ADPR occurs N-terminally. Zebrafish TRPM2 needs both, the N-terminal ADPR-binding pocket and NUDT9H. Our aim was to pinpoint the relative functional contributions of NUDT9H and the N-terminal ADPR-binding pocket in zebrafish TRPM2, to identify fundamental mechanisms of ADPR-directed gating. We show that the NUDT9H domains of human and zebrafish TRPM2 are interchangeable since chimeras generate ADPR-sensitive channels. A point mutation at a highly conserved position within NUDT9H induces loss-of-function in both vertebrate channels. The substrate specificity of zebrafish TRPM2 corresponds to that of sea anemone TRPM2, indicating gating by the proposed N-terminal ADPR-binding pocket. However, a point mutation in this region abolishes ADPR activation also in human TRPM2. These findings provide functional evidence for an uniform N-terminal ADPR-binding pocket in TRPM2 of zebrafish and sea anemone with modified function in human TRPM2. The structural importance of NUDT9H in vertebrate TRPM2 can be associated with a single amino acid residue which is not directly involved in the binding of ADPR. LA - English DB - MTMT ER - TY - JOUR AU - Yin, Ying AU - Wu, Mengyu AU - Hsw, Allen L. AU - Borschel, William F. AU - Borgnia, Mario J. AU - Lander, Gabriel C. AU - Lee, Seok-Yong TI - Visualizing structural transitions of ligand-dependent gating of the TRPM2 channel JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 10 PY - 2019 PG - 14 SN - 2041-1723 DO - 10.1038/s41467-019-11733-5 UR - https://m2.mtmt.hu/api/publication/30789149 ID - 30789149 N1 - Funding Agency and Grant Number: National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R35NS097241, DP2EB020402, R21AR072910]; National Institutes of Health Intramural Research ProgramUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA; US National Institute of Environmental Health SciencesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS) [ZIC ES103326]; Pew Charitable Trusts; AmgenAmgen; National Science Foundation Graduate Student Research FellowshipNational Science Foundation (NSF); NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [S10OD021634] Funding text: Cryo-EM data for TRPM2DR_Ca2+ were collected at The Scripps Research Institute (TSRI) electron microscopy facility. Cryo-EM data for TRPM2DR_Apo and TRPM2DR_ADPR/Ca2+ were collected at the Duke Shared Materials Instrumentation Facility (SMIF). Preliminary cryo-EM work, including sample screening, was performed at the cryo-EM facility at NIEHS. We thank J.C. Ducom at the TSRI High Performance Computing facility for computational support and B. Anderson for microscope support. We thank L. Zubcevic, A. Bartesaghi, and L. Csanady for providing critical manuscript reading, developing a routine for preprocessing, and preliminary functional studies, respectively. This work was supported by the National Institutes of Health (R35NS097241 to S.-Y.L., DP2EB020402 and R21AR072910 to G.C.L.) and by the National Institutes of Health Intramural Research Program; US National Institute of Environmental Health Sciences (ZIC ES103326 to M.J.B). G.C.L is supported as a Searle Scholar, a Pew Scholar in the Biomedical Sciences, supported by the Pew Charitable Trusts, and by an Amgen Young Investigator award. M.W is supported by a National Science Foundation Graduate Student Research Fellowship. Computational analyses of EM data were performed using shared instrumentation funded by NIH S10OD021634. Export Date: 7 January 2020 Correspondence Address: Lee, S.-Y.; Department of Biochemistry, Duke University School of MedicineUnited States; email: seok-yong.lee@duke.edu Export Date: 8 January 2020 Correspondence Address: Lee, S.-Y.; Department of Biochemistry, Duke University School of MedicineUnited States; email: seok-yong.lee@duke.edu Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, United States Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, United States Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, United States Cited By :1 Export Date: 14 February 2020 Correspondence Address: Lee, S.-Y.; Department of Biochemistry, Duke University School of MedicineUnited States; email: seok-yong.lee@duke.edu Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; calcium, 7440-70-2, 14092-94-5; Adenosine Diphosphate Ribose; Calcium; TRPM Cation Channels Funding details: National Science Foundation, NSF Funding details: S10OD021634 Funding details: National Health Research Institutes, NHRI Funding details: National Institutes of Health, NIH, DP2EB020402, R21AR072910, R35NS097241 Funding details: Amgen Funding details: National Institute of Environmental Health Sciences, NIEHS, ZIC ES103326 Funding details: Pew Charitable Trusts, The Pew Charitable Trusts Funding text 1: Cryo-EM data for TRPM2DR_Ca2+ were collected at The Scripps Research Institute (TSRI) electron microscopy facility. Cryo-EM data for TRPM2DR_Apoand TRPM2DR_ADPR/Ca2+ were collected at the Duke Shared Materials Instrumentation Facility (SMIF). Preliminary cryo-EM work, including sample screening, was performed at the cryo-EM facility at NIEHS. We thank J.C. Ducom at the TSRI High Performance Computing facility for computational support and B. Anderson for microscope support. We thank L. Zubcevic, A. Bartesaghi, and L. Csanady for providing critical manuscript reading, developing a routine for preprocessing, and preliminary functional studies, respectively. This work was supported by the National Institutes of Health (R35NS097241 to S.-Y.L., DP2EB020402 and R21AR072910 to G.C.L.) and by the National Institutes of Health Intramural Research Program; US National Institute of Environmental Health Sciences (ZIC ES103326 to M.J.B). G.C.L is supported as a Searle Scholar, a Pew Scholar in the Biomedical Sciences, supported by the Pew Charitable Trusts, and by an Amgen Young Investigator award. M.W is supported by a National Science Foundation Graduate Student Research Fellowship. Computational analyses of EM data were performed using shared instrumentation funded by NIH S10OD021634. Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, United States Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, United States Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, United States Cited By :4 Export Date: 1 July 2020 Correspondence Address: Lee, S.-Y.; Department of Biochemistry, Duke University School of MedicineUnited States; email: seok-yong.lee@duke.edu Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; calcium, 7440-70-2, 14092-94-5; Adenosine Diphosphate Ribose; Calcium; TRPM Cation Channels Funding details: National Science Foundation, NSF Funding details: National Institute of Environmental Health Sciences, NIEHS, ZIC ES103326 Funding details: National Institutes of Health, NIH, DP2EB020402, R21AR072910, R35NS097241 Funding details: National Institutes of Health, NIH, S10OD021634 Funding details: Pew Charitable Trusts Funding text 1: Cryo-EM data for TRPM2DR_Ca2+ were collected at The Scripps Research Institute (TSRI) electron microscopy facility. Cryo-EM data for TRPM2DR_Apoand TRPM2DR_ADPR/Ca2+ were collected at the Duke Shared Materials Instrumentation Facility (SMIF). Preliminary cryo-EM work, including sample screening, was performed at the cryo-EM facility at NIEHS. We thank J.C. Ducom at the TSRI High Performance Computing facility for computational support and B. Anderson for microscope support. We thank L. Zubcevic, A. Bartesaghi, and L. Csanady for providing critical manuscript reading, developing a routine for preprocessing, and preliminary functional studies, respectively. This work was supported by the National Institutes of Health (R35NS097241 to S.-Y.L., DP2EB020402 and R21AR072910 to G.C.L.) and by the National Institutes of Health Intramural Research Program; US National Institute of Environmental Health Sciences (ZIC ES103326 to M.J.B). G.C.L is supported as a Searle Scholar, a Pew Scholar in the Biomedical Sciences, supported by the Pew Charitable Trusts, and by an Amgen Young Investigator award. M.W is supported by a National Science Foundation Graduate Student Research Fellowship. Computational analyses of EM data were performed using shared instrumentation funded by NIH S10OD021634. AB - The transient receptor potential melastatin 2 (TRPM2) channel plays a key role in redox sensation in many cell types. Channel activation requires binding of both ADP-ribose (ADPR) and Ca2+. The recently published TRPM2 structures from Danio rerio in the ligand-free and the ADPR/Ca2+-bound conditions represent the channel in closed and open states, which uncovered substantial tertiary and quaternary conformational rearrangements. However, it is unclear how these rearrangements are achieved within the tetrameric channel during channel gating. Here we report the cryo-electron microscopy structures of Danio rerio TRPM2 in the absence of ligands, in complex with Ca2+ alone, and with both ADPR and Ca2+, resolved to similar to 4.3 angstrom, similar to 3.8 angstrom, and similar to 4.2 angstrom, respectively. In contrast to the published results, our studies capture ligand-bound TRPM2 structures in two-fold symmetric intermediate states, offering a glimpse of the structural transitions that bridge the closed and open conformations. LA - English DB - MTMT ER - TY - JOUR AU - Yu, Peilin AU - Liu, Zhenming AU - Yu, Xiafei AU - Ye, Peiwu AU - Liu, Huan AU - Xue, Xiwen AU - Yang, Lixin AU - Li, Zhongtang AU - Wu, Yang AU - Fang, Cheng AU - Zhao, Yong Juan AU - Yang, Fan AU - Luo, Jian Hong AU - Jiang, Lin-Hua AU - Zhang, Liangren AU - Zhang, Lihe AU - Yang, Wei TI - Direct Gating of the TRPM2 Channel by cADPR via Specific Interactions with the ADPR Binding Pocket JF - CELL REPORTS J2 - CELL REP VL - 27 PY - 2019 IS - 12 SP - 3684 EP - + PG - 16 SN - 2211-1247 DO - 10.1016/j.celrep.2019.05.067 UR - https://m2.mtmt.hu/api/publication/30766408 ID - 30766408 N1 - Funding Agency and Grant Number: Natural Science Foundation of ChinaNational Natural Science Foundation of China [81371302, 81571127, 31872796, 31471118, 21572010, 21772005, 31800990, 81673279, 81573273]; National Basic Research Program of ChinaNational Basic Research Program of China [2014CB910300]; National Major New Drugs Innovation and Development [2018ZX09711001004-005]; Zhejiang Provincial Natural Science FoundationNatural Science Foundation of Zhejiang Province [LR16H090001, LY19B020013]; 111 ProjectMinistry of Education, China - 111 Project; non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2017PT31038, 2018PT31041]; University of Leeds-Zhejiang University Strategic Collaboration Partnership Programme Funding text: We thank Prof. Jie Zheng for constructive discussion. This work was supported by grants from the Natural Science Foundation of China (81371302, 81571127, 31872796, 31471118, 21572010, 21772005, 31800990, 81673279, and 81573273); the National Basic Research Program of China (2014CB910300); National Major New Drugs Innovation and Development (2018ZX09711001004-005); Zhejiang Provincial Natural Science Foundation (LR16H090001, LY19B020013); the 111 Project; the non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2017PT31038, 2018PT31041); and University of Leeds-Zhejiang University Strategic Collaboration Partnership Programme. Export Date: 7 January 2020 Correspondence Address: Yang, W.; Department of Biophysics, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of MedicineChina; email: yangwei@zju.edu.cn Export Date: 8 January 2020 Correspondence Address: Yang, W.; Department of Biophysics, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of MedicineChina; email: yangwei@zju.edu.cn AB - cADPR is a well-recognized signaling molecule by modulating the RyRs, but considerable debate exists regarding whether cADPR can bind to and gate the TRPM2 channel, which mediates oxidative stress signaling in diverse physiological and pathological processes. Here, we show that purified cADPR evoked TRPM2 channel currents in both whole-cell and cell-free single-channel recordings and specific binding of cADPR to the purified NUDT9-H domain of TRPM2 by surface plasmon resonance. Furthermore, by combining computational modeling with electrophysiological recordings, we show that the TRPM2 channels carrying point mutations at H1346, T1347, L1379, S1391, E1409, and L1484 possess distinct sensitivity profiles for ADPR and cADPR. These results clearly indicate cADPR is a bona fide activator at the TRPM2 channel and clearly delineate the structural basis for cADPR binding, which not only lead to a better understanding in the gating mechanism of TRPM2 channel but also shed light on a cADPR-induced RyRs-independent Ca2+ signaling mechanism. LA - English DB - MTMT ER - TY - JOUR AU - Belrose, Jillian Corinne AU - Jackson, Michael Frederick TI - TRPM2: a candidate therapeutic target for treating neurological diseases JF - ACTA PHARMACOLOGICA SINICA J2 - ACTA PHARMACOL SIN VL - 39 PY - 2018 IS - 5 SP - 722 EP - 732 PG - 11 SN - 1671-4083 DO - 10.1038/aps.2018.31 UR - https://m2.mtmt.hu/api/publication/27589469 ID - 27589469 N1 - Funding Agency and Grant Number: Canadian Institutes for Health Research CIHRCanadian Institutes of Health Research (CIHR) [MOP-125901, MOP-97771] Funding text: This work was supported by the Canadian Institutes for Health Research CIHR (grants MOP-125901 and MOP-97771 to Michael Frederick JACKSON). Export Date: 8 January 2020 CODEN: APSCG Correspondence Address: Jackson, M.F.; Department of Pharmacology and Therapeutics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of ManitobaCanada; email: michael.jackson@umanitoba.ca LA - English DB - MTMT ER - TY - JOUR AU - Huang, Yihe AU - Winkler, Paige A. AU - Sun, Weinan AU - Lu, Wei AU - Du, Juan TI - Architecture of the TRPM2 channel and its activation mechanism by ADP-ribose and calcium JF - NATURE J2 - NATURE VL - 562 PY - 2018 IS - 7725 SP - 145 EP - + PG - 17 SN - 0028-0836 DO - 10.1038/s41586-018-0558-4 UR - https://m2.mtmt.hu/api/publication/30538832 ID - 30538832 N1 - Van Andel Research Institute, Grand Rapids, MI, United States Vollum Institute, Oregon Health & Science University, Portland, OR, United States Janelia Research Campus, Ashburn, VA, United States Cited By :18 Export Date: 28 August 2019 CODEN: NATUA Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; calcium, 7440-70-2, 14092-94-5; calcium ion, 14127-61-8; edetic acid, 150-43-6, 60-00-4; inorganic pyrophosphatase, 9024-82-2, 9033-44-7; Adenosine Diphosphate Ribose; Apoproteins; Calcium; Edetic Acid; Ligands; NUDT10 protein, human; Pyrophosphatases; TRPM Cation Channels; Zebrafish Proteins Funding details: Van Andel Research Institute Funding text 1: Acknowledgements We thank G. Zhao and X. Meng for support with data collection at the David Van Andel Advanced Cryo-Electron Microscopy Suite, the HPC team in the Van Andel Research Institute (VARI) for computational support, C. Xu for help with SerialEM, and D. Nadziejka for technical editing. This work was supported by internal VARI funding. Van Andel Research Institute, Grand Rapids, MI, United States Vollum Institute, Oregon Health & Science University, Portland, OR, United States Janelia Research Campus, Ashburn, VA, United States Cited By :24 Export Date: 31 October 2019 CODEN: NATUA Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; calcium, 7440-70-2, 14092-94-5; calcium ion, 14127-61-8; edetic acid, 150-43-6, 60-00-4; inorganic pyrophosphatase, 9024-82-2, 9033-44-7; Adenosine Diphosphate Ribose; Apoproteins; Calcium; Edetic Acid; Ligands; NUDT10 protein, human; Pyrophosphatases; TRPM Cation Channels; Zebrafish Proteins Funding details: Van Andel Research Institute Funding text 1: Acknowledgements We thank G. Zhao and X. Meng for support with data collection at the David Van Andel Advanced Cryo-Electron Microscopy Suite, the HPC team in the Van Andel Research Institute (VARI) for computational support, C. Xu for help with SerialEM, and D. Nadziejka for technical editing. This work was supported by internal VARI funding. Funding Agency and Grant Number: internal VARI funding Funding text: We thank G. Zhao and X. Meng for support with data collection at the David Van Andel Advanced Cryo-Electron Microscopy Suite, the HPC team in the Van Andel Research Institute (VARI) for computational support, C. Xu for help with SerialEM, and D. Nadziejka for technical editing. This work was supported by internal VARI funding. Export Date: 7 January 2020 CODEN: NATUA Export Date: 8 January 2020 CODEN: NATUA AB - Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable, non-selective cation channel that has an essential role in diverse physiological processes such as core body temperature regulation, immune response and apoptosis(1-4). TRPM2 is polymodal and can be activated by a wide range of stimuli(1-7), including temperature, oxidative stress and NAD(+)-related metabolites such as ADP-ribose (ADPR). Its activation results in both Ca2+ entry across the plasma membrane and Ca2+ release from lysosomes(8), and has been linked to diseases such as ischaemia-reperfusion injury, bipolar disorder and Alzheimer's disease(9-11). Here we report the cryo-electron microscopy structures of the zebrafish TRPM2 in the apo resting (closed) state and in the ADPR/Ca2+-bound active (open) state, in which the characteristic NUDT9-H domains hang underneath the MHR1/2 domain. We identify an ADPR-binding site located in the bi-lobed structure of the MHR1/2 domain. Our results provide an insight into the mechanism of activation of the TRPM channel family and define a framework for the development of therapeutic agents to treat neurodegenerative diseases and temperature-related pathological conditions. LA - English DB - MTMT ER - TY - JOUR AU - Kheradpezhouh, E AU - Zhou, FH AU - Barritt, GJ AU - Rychkov, GY TI - Oxidative stress promotes redistribution of TRPM2 channels to the plasma membrane in hepatocytes JF - BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS J2 - BIOCHEM BIOPH RES CO VL - 503 PY - 2018 IS - 3 SP - 1891 EP - 1896 PG - 6 SN - 0006-291X DO - 10.1016/j.bbrc.2018.07.132 UR - https://m2.mtmt.hu/api/publication/27692935 ID - 27692935 N1 - Funding Agency and Grant Number: NHMRC, AustraliaNational Health and Medical Research Council of Australia [APP1086817] Funding text: We thank Prof Yasuo Mon for providing TRPM2 KO mouse and TRPM2 cDNA. This work was supported by NHMRC, Australia (APP1086817). Export Date: 8 January 2020 CODEN: BBRCA Correspondence Address: Rychkov, G.Y.; School of Medicine, The University of AdelaideAustralia; email: grigori.rychkov@adelaide.edu.au LA - English DB - MTMT ER - TY - JOUR AU - Tan, Chun-Hsiang AU - McNaughton, Peter A TI - TRPM2 and warmth sensation JF - PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY J2 - PFLUG ARCH EUR J PHY VL - 470 PY - 2018 IS - 5 SP - 787 EP - 798 PG - 12 SN - 0031-6768 DO - 10.1007/s00424-018-2139-7 UR - https://m2.mtmt.hu/api/publication/27589544 ID - 27589544 N1 - Journal Article; Review Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, Guy’s Campus, King’s College London, London, SE1 1UL, United Kingdom Export Date: 28 August 2019 CODEN: PFLAB Correspondence Address: McNaughton, P.A.; Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, Guy’s Campus, King’s College LondonUnited Kingdom; email: peter.mcnaughton@kcl.ac.uk Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; hydrogen peroxide, 7722-84-1; inorganic pyrophosphatase, 9024-82-2, 9033-44-7; TRPM Cation Channels Funding Agency and Grant Number: Biotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research Council (BBSRC) [BB/L002787/1] Export Date: 7 January 2020 CODEN: PFLAB Correspondence Address: McNaughton, P.A.; Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, Guy’s Campus, King’s College LondonUnited Kingdom; email: peter.mcnaughton@kcl.ac.uk Export Date: 8 January 2020 CODEN: PFLAB Correspondence Address: McNaughton, P.A.; Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, Guy’s Campus, King’s College LondonUnited Kingdom; email: peter.mcnaughton@kcl.ac.uk LA - English DB - MTMT ER - TY - JOUR AU - Wang, Longfei AU - Fu, Tian-Min AU - Zhou, Yiming AU - Xia, Shiyu AU - Greka, Anna AU - Wu, Hao TI - Structures and gating mechanism of human TRPM2 JF - SCIENCE J2 - SCIENCE VL - 362 PY - 2018 IS - 6421 PG - 8 SN - 0036-8075 DO - 10.1126/science.aav4809 UR - https://m2.mtmt.hu/api/publication/30519709 ID - 30519709 N1 - Funding Agency and Grant Number: NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [DK095045, DK099465, DK103658] Funding text: This work is supported by NIH grants DK095045, DK099465, and DK103658 to A.G. Export Date: 8 January 2020 CODEN: SCIEA Correspondence Address: Fu, T.-M.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical SchoolUnited States; email: tianmin.fu@childrens.harvard.edu AB - Transient receptor potential (TRP) melastatin 2 (TRPM2) is a cation channel associated with numerous diseases. It has a C-terminal NUDT9 homology (NUDT9H) domain responsible for binding adenosine diphosphate (ADP) ribose (ADPR), and both ADPR and calcium (Ca2+) are required for TRPM2 activation. Here we report cryo electron microscopy structures of human TRPM2 alone, with ADPR, and with ADPR and Ca2+. NUDT9H forms both intra-and intersubunit interactions with the N-terminal TRPM homology region (MHR1/2/3) in the apo state but undergoes conformational changes upon ADPR binding, resulting in rotation of MHR1/2 and disruption of the intersubunit interaction. The binding of Ca2+ further engages transmembrane helices and the conserved TRP helix to cause conformational changes at the MHR arm and the lower gating pore to potentiate channel opening. These findings explain the molecular mechanism of concerted TRPM2 gating by ADPR and Ca2+ and provide insights into the gating mechanism of other TRP channels. LA - English DB - MTMT ER - TY - CHAP AU - Kashio, Makiko AU - Tominaga, Makoto ED - Mohammed, Awad Ali Khalid TI - Redox-Sensitive TRP Channels: TRPA1 and TRPM2 T2 - Redox PB - IntechOpen CY - London SN - 9789535133933 PY - 2017 SP - online DO - 10.5772/intechopen.69202 UR - https://m2.mtmt.hu/api/publication/30642562 ID - 30642562 LA - English DB - MTMT ER - TY - JOUR AU - Kashio, Makiko AU - Tominaga, Makoto TI - The TRPM2 channel: A thermo-sensitive metabolic sensor JF - CHANNELS J2 - CHANNELS VL - 11 PY - 2017 IS - 5 SP - 426 EP - 433 PG - 8 SN - 1933-6950 DO - 10.1080/19336950.2017.1344801 UR - https://m2.mtmt.hu/api/publication/27095257 ID - 27095257 N1 - Funding Agency and Grant Number: Ministry of Education, Culture, Sports, Science and Technology in JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [15H02501, 15H05928, 15K18974, 17K08543]; Salt Science and Mishima Kaiun Memorial Foundation [1634] Funding text: This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology in Japan (#15H02501 and #15H05928 to MT, and #15K18974 and #17K08543 to MK) and by Salt Science (#1634) and Mishima Kaiun Memorial Foundation to MK. Export Date: 7 January 2020 Correspondence Address: Tominaga, M.; Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), Higashiyama 5–1, Myodaiji, Japan; email: tominaga@nips.ac.jp Export Date: 8 January 2020 Correspondence Address: Tominaga, M.; Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), Higashiyama 5–1, Myodaiji, Japan; email: tominaga@nips.ac.jp LA - English DB - MTMT ER - TY - JOUR AU - Kuehn, Frank AU - Kuehn, Cornelia AU - Lueckhoff, Andreas TI - Different Principles of ADP-Ribose-Mediated Activation and Opposite Roles of the NUDT9 Homology Domain in the TRPM2 Orthologs of Man and Sea Anemone JF - FRONTIERS IN PHYSIOLOGY J2 - FRONT PHYSIOL VL - 8 PY - 2017 PG - 14 SN - 1664-042X DO - 10.3389/fphys.2017.00879 UR - https://m2.mtmt.hu/api/publication/27095255 ID - 27095255 LA - English DB - MTMT ER - TY - JOUR AU - Kuehn, Frank J P AU - Mathis, Winking AU - Cornelia, Kuehn AU - Hoffmann, Daniel C AU - Lueckhoff, Andreas TI - Modulation of activation and inactivation by Ca2+ and 2-APB in the pore of an archetypal TRPM channel from Nematostella vectensis JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 7 PY - 2017 PG - 13 SN - 2045-2322 DO - 10.1038/s41598-017-07652-4 UR - https://m2.mtmt.hu/api/publication/26932128 ID - 26932128 N1 - Export Date: 12 June 2019 Cited By :5 Export Date: 5 September 2019 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Medical Faculty, RWTH AachenGermany; email: fkuehn@ukaachen.de Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; 2-aminoethyl diphenylborinate; Boron Compounds; Calcium; TRPM Cation Channels Funding Agency and Grant Number: Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [DFG KU 2271/4-1] Funding text: We thank Marina Wolf for expert technical assistance. The study was supported by the Deutsche Forschungsgemeinschaft (DFG KU 2271/4-1). Export Date: 7 January 2020 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Medical Faculty, RWTH AachenGermany; email: fkuehn@ukaachen.de Export Date: 8 January 2020 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Medical Faculty, RWTH AachenGermany; email: fkuehn@ukaachen.de LA - English DB - MTMT ER - TY - JOUR AU - Kühn, Frank JP TI - New insights into the interaction between ADP-ribose and human TRPM2 channel JF - Biotarget VL - 2017 PY - 2017 IS - 1 PG - 4 SN - 2522-669X DO - 10.21037/biotarget.2017.10.01 UR - https://m2.mtmt.hu/api/publication/30642422 ID - 30642422 LA - English DB - MTMT ER - TY - JOUR AU - Pires, Paulo Wagner AU - Earley, Scott TI - Redox regulation of transient receptor potential channels in the endothelium JF - MICROCIRCULATION J2 - MICROCIRCULATION VL - 24 PY - 2017 IS - 3 PG - 10 SN - 1073-9688 DO - 10.1111/micc.12329 UR - https://m2.mtmt.hu/api/publication/26764281 ID - 26764281 N1 - Funding Agency and Grant Number: American Heart AssociationAmerican Heart Association [15POST24720002]; National Heart, Lung and Blood InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01HL091905] Funding text: The present manuscript was supported by the American Heart Association (15POST24720002 to PWP) and the National Heart, Lung and Blood Institute (R01HL091905 to SE). Export Date: 8 January 2020 CODEN: MROCE Correspondence Address: Earley, S.; Department of Pharmacology, Cardiovascular Research Center, Reno School of Medicine, University of NevadaUnited States; email: searley@medicine.nevada.edu LA - English DB - MTMT ER - TY - JOUR AU - Srouji, JR AU - Xu, A AU - Park, A AU - Kirsch, JF AU - Brenner, SE TI - The evolution of function within the Nudix homology clan JF - PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS J2 - PROTEINS VL - 85 PY - 2017 IS - 5 SP - 775 EP - 811 PG - 37 SN - 0887-3585 DO - 10.1002/prot.25223 UR - https://m2.mtmt.hu/api/publication/26622637 ID - 26622637 N1 - Funding Agency and Grant Number: National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIH R01 GM071749, R01 GM071749-03S2] Funding text: The authors would like to thank Barbara E. Engelhardt for advice and assistance, Emma Ganley for her guidance in approaching the structure-induced sequence alignment, and Daniel Chao for his contribution on collecting experimental characterization data of Nudix homology proteins. This research was supported by the National Institutes of Health (NIH R01 GM071749 and R01 GM071749-03S2). Export Date: 8 January 2020 Correspondence Address: Brenner, S.E.; Plant and Microbial Biology Department, University of CaliforniaUnited States; email: brenner@compbio.berkeley.edu LA - English DB - MTMT ER - TY - JOUR AU - Yu, P AU - Xue, X AU - Zhang, J AU - Hu, X AU - Wu, Y AU - Jiang, L-H AU - Jin, H AU - Luo, J AU - Zhang, L AU - Liu, Z AU - Yang, W TI - Identification of the ADPR binding pocket in the NUDT9 homology domain of TRPM2 JF - JOURNAL OF GENERAL PHYSIOLOGY J2 - J GEN PHYSIOL VL - 149 PY - 2017 IS - 2 SP - 219 EP - 235 PG - 17 SN - 0022-1295 DO - 10.1085/jgp.201611675 UR - https://m2.mtmt.hu/api/publication/26497564 ID - 26497564 N1 - Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, 310058, China State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, England, LS2 9JT, United Kingdom Department of Physiology and Neurobiology, Xinxiang Medical University, Henan, 453003, China Sino-UK Brain Function Laboratory, Xinxiang Medical University, Henan, 453003, China Cited By :16 Export Date: 20 September 2019 CODEN: JGPLA Correspondence Address: Yang, W.; Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang University School of MedicineChina; email: yangwei@zju.edu.cn Funding Agency and Grant Number: National Basic Research Program of ChinaNational Basic Research Program of China [2013CB910204, 2014CB910300]; Natural Science Foundation of ChinaNational Natural Science Foundation of China [21402171] Funding text: This work was supported by grants from the National Basic Research Program of China (2013CB910204 to W. Yang and 2014CB910300 to J. Luo) and the Natural Science Foundation of China (21402171 to P. Yu). Export Date: 7 January 2020 CODEN: JGPLA Correspondence Address: Yang, W.; Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang University School of MedicineChina; email: yangwei@zju.edu.cn Export Date: 8 January 2020 CODEN: JGPLA Correspondence Address: Yang, W.; Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang University School of MedicineChina; email: yangwei@zju.edu.cn LA - English DB - MTMT ER - TY - JOUR AU - Zierler, Susanna AU - Hampe, Sarah AU - Nadolni, Wiebke TI - TRPM channels as potential therapeutic targets against pro-inflammatory diseases JF - CELL CALCIUM J2 - CELL CALCIUM VL - 67 PY - 2017 SP - 105 EP - 115 PG - 11 SN - 0143-4160 DO - 10.1016/j.ceca.2017.05.002 UR - https://m2.mtmt.hu/api/publication/27095254 ID - 27095254 N1 - Funding Agency and Grant Number: Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [TRR 152/1]; Marie-Curie Fellowship (REA) Funding text: We thank Lynda Addington for critical reading of the manuscript. Images were designed using Servier Medical Art by Servier, which is licensed under a Creative Commons Attribution 3.0 Unported License. SZ was supported by the Deutsche Forschungsgemeinschaft (TRR 152/1) and a Marie-Curie Fellowship (REA) FP7-PEOPLE-2012-CIG. Export Date: 7 January 2020 CODEN: CECAD Correspondence Address: Zierler, S.; Walther Straub Institute of Pharmacology and Toxicology, LMU MunichGermany; email: susanna.zierler@lrz.uni-muenchen.de Export Date: 8 January 2020 CODEN: CECAD Correspondence Address: Zierler, S.; Walther Straub Institute of Pharmacology and Toxicology, LMU MunichGermany; email: susanna.zierler@lrz.uni-muenchen.de LA - English DB - MTMT ER -