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 - Munaron, Luca AU - Chinigo, Giorgia AU - Scarpellino, Giorgia AU - Ruffinatti, Federico Alessandro TI - The fallacy of functional nomenclature in the kingdom of biological multifunctionality: physiological and evolutionary considerations on ion channels JF - JOURNAL OF PHYSIOLOGY-LONDON J2 - J PHYSIOL-LONDON PY - 2023 PG - 15 SN - 0022-3751 DO - 10.1113/JP284422 UR - https://m2.mtmt.hu/api/publication/34235533 ID - 34235533 AB - Living organisms are multiscale complex systems that have evolved high degrees of multifunctionality and redundancy in the structure-function relationship. A number of factors, only in part determined genetically, affect the jobs of proteins. The overall structural organization confers unique molecular properties that provide the potential to perform a pattern of activities, some of which are co-opted by specific environments. The variety of multifunctional proteins is expanding, but most cases are handled individually and according to the still dominant 'one structure-one function' approach, which relies on the attribution of canonical names typically referring to the first task identified for a given protein. The present topical review focuses on the multifunctionality of ion channels as a paradigmatic example. Mounting evidence reports the ability of many ion channels (including members of voltage-dependent, ligand-gated and transient receptor potential families) to exert biological effects independently of their ion conductivity. 'Functionally based' nomenclature (the practice of naming a protein or family of proteins based on a single purpose) is a conceptual bias for three main reasons: (i) it increases the amount of ambiguity, deceiving our understanding of the multiple contributions of biomolecules that is the heart of the complexity; (ii) it is in stark contrast to protein evolution dynamics, largely based on multidomain arrangement; and (iii) it overlooks the crucial role played by the microenvironment in adjusting the actions of cell structures and in tuning protein isoform diversity to accomplish adaptational requirements. Biological information in protein physiology is distributed among different entwined layers working as the primary 'locus' of natural selection and of evolutionary constraints.imageAbstract figure legend Different features underlying the multifunctional nature of ion channels. image LA - English DB - MTMT ER - TY - JOUR AU - Vydra Bousova, Kristyna AU - Zouharova, Monika AU - Jiraskova, Katerina AU - Vetyskova, Veronika TI - Interaction of Calmodulin with TRPM: An Initiator of Channel Modulation JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 20 SN - 1661-6596 DO - 10.3390/ijms242015162 UR - https://m2.mtmt.hu/api/publication/34487828 ID - 34487828 N1 - Export Date: 28 February 2024 AB - Transient receptor potential melastatin (TRPM) channels, a subfamily of the TRP superfamily, constitute a diverse group of ion channels involved in mediating crucial cellular processes like calcium homeostasis. These channels exhibit complex regulation, and one of the key regulatory mechanisms involves their interaction with calmodulin (CaM), a cytosol ubiquitous calcium-binding protein. The association between TRPM channels and CaM relies on the presence of specific CaM-binding domains in the channel structure. Upon CaM binding, the channel undergoes direct and/or allosteric structural changes and triggers down- or up-stream signaling pathways. According to current knowledge, ion channel members TRPM2, TRPM3, TRPM4, and TRPM6 are directly modulated by CaM, resulting in their activation or inhibition. This review specifically focuses on the interplay between TRPM channels and CaM and summarizes the current known effects of CaM interactions and modulations on TRPM channels in cellular physiology. LA - English DB - MTMT ER - TY - JOUR AU - Bartók, Ádám AU - Csanády, László TI - Dual amplification strategy turns TRPM2 channels into supersensitive central heat detectors JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA J2 - P NATL ACAD SCI USA VL - 119 PY - 2022 IS - 48 PG - 11 SN - 0027-8424 DO - 10.1073/pnas.2212378119 UR - https://m2.mtmt.hu/api/publication/33262968 ID - 33262968 N1 - Hungarian Centre of Excellence for Molecular Medicine-Semmelweis Egyetem (HCEMM-SE), Molecular Channelopathies Research Group, Semmelweis University, Budapest, H-1094, Hungary Magyar Tudományos Akadémia-Semmelweis Egyetem (MTA-SE), Ion Channel Research Group, Semmelweis University, Budapest, H-1094, Hungary Department of Biochemistry, Semmelweis University, Budapest, H-1094, Hungary Cited By :3 Export Date: 4 September 2023 CODEN: PNASA Correspondence Address: Csanády, L.; Hungarian Centre of Excellence for Molecular Medicine-Semmelweis Egyetem (HCEMM-SE), Hungary; email: csanady.laszlo@med.semmelweis-univ.hu Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; calcium ion, 14127-61-8; hydrogen peroxide, 7722-84-1; calcium, 7440-70-2, 14092-94-5; Adenosine Diphosphate Ribose; Calcium; Hydrogen Peroxide; TRPM Cation Channels Funding details: 739593 Funding details: GINOP-2.3.2-15-2016-00051 Funding details: ÚNKP-20-5-SE-6, ÚNKP-21-5-SE-10 Funding details: Magyar Tudományos Akadémia, MTA, BO/00103/20, LP2017-14/2017 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH Funding text 1: We thank Beáta Töröcsik for subcloning T5L-TRPM2 into pcDNA3, Iordan Iordanov for providing purified nvNUDT9H, and Katalin Zboray (Agricultural Institute, Centre for Agricultural Research, Martonvásár, Hungary) for providing the stable T5L TRPM2 cell line (Economic Development and Innovation Operational Programme (GINOP-2.3.2-15-2016-00051) of the National Research, Development and Innovation Office). Support was provided by EU Horizon 2020 Research and Innovation Program grant 739593 and MTA Lendület grant LP2017-14/2017 to L.C. and a New National Excellence Program (ÚNKP) award of the Ministry of Human Capacities of Hungary to Semmelweis University. Á.B. was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00103/20) and the New National Excellence Program (ÚNKP) Bolyai+ scholarship of the Ministry of Human Capacities of Hungary (ÚNKP-20-5-SE-6 and ÚNKP-21-5-SE-10). Funding text 2: ACKNOWLEDGMENTS. We thank Beáta Töröcsik for subcloning T5L-TRPM2 into pcDNA3, Iordan Iordanov for providing purified nvNUDT9H, and Katalin Zboray (Agricultural Institute, Centre for Agricultural Research, Martonvásár, Hungary) for providing the stableT5LTRPM2 cell line (Economic Development and Innovation Operational Programme (GINOP-2.3.2-15-2016-00051) of the National Research, Development and Innovation Office). Support was provided by EU Horizon 2020 Research and Innovation Program grant 739593 and MTA Lendület grant LP2017-14/2017 to L.C. and a New National Excellence Program (ÚNKP) award of the Ministry of Human Capacities of Hungary to Semmelweis University. Á.B. was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00103/20) and the New National Excellence Program (ÚNKP) Bolyai+ scholarship of the Ministry of Human Capacities of Hungary (ÚNKP-20-5-SE-6 and ÚNKP-21-5-SE-10). AB - The Ca 2+ and ADP ribose (ADPR)-activated cation channel TRPM2 is the closest homolog of the cold sensor TRPM8 but serves as a deep-brain warmth sensor. To unravel the molecular mechanism of heat sensing by the TRPM2 protein, we study here temperature dependence of TRPM2 currents in cell-free membrane patches across ranges of agonist concentrations. We find that channel gating remains strictly agonist-dependent even at 40°C: heating alone or in combination with just Ca 2+ , just ADPR, Ca 2+ + cyclic ADPR, or H 2 O 2 pretreatment only marginally activates TRPM2. For fully liganded TRPM2, pore opening is intrinsically endothermic, due to ~10-fold larger activation enthalpy for opening (~200 kJ/mol) than for closure (~20 kJ/mol). However, the temperature threshold is too high (>40°C) for unliganded but too low (<15°C) for fully liganded channels. Thus, warmth sensitivity around 37°C is restricted to narrow ranges of agonist concentrations. For ADPR, that range matches, but for Ca 2+ , it exceeds bulk cytosolic values. The supraphysiological [Ca 2+ ] needed for TRPM2 warmth sensitivity is provided by Ca 2+ entering through the channel’s pore. That positive feedback provides further strong amplification to the TRPM2 temperature response (Q 10 ~ 1,000), enabling the TRPM2 protein to autonomously respond to tiny temperature fluctuations around 37°C. These functional data together with published structures suggest a molecular mechanism for opposite temperature dependences of two closely related channel proteins. LA - English DB - MTMT ER - TY - JOUR AU - Barth, D. AU - Lückhoff, A. AU - Kühn, F.J.P. TI - Species-specific regulation of trpm2 by pi(4,5)p2 via the membrane interfacial cavity JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 22 PY - 2021 IS - 9 SN - 1661-6596 DO - 10.3390/ijms22094637 UR - https://m2.mtmt.hu/api/publication/32008293 ID - 32008293 N1 - Export Date: 11 May 2021 Correspondence Address: Barth, D.; Institute of Physiology, Germany; email: dbarth@ukaachen.de Funding details: Deutsche Forschungsgemeinschaft, DFG, KU Funding details: Deutsche Forschungsgemeinschaft, DFG Funding text 1: by the Deutsche Forschungsgemeinschaft (DFG, Grant KU Export Date: 13 May 2021 Correspondence Address: Barth, D.; Institute of Physiology, Germany; email: dbarth@ukaachen.de Funding details: Deutsche Forschungsgemeinschaft, DFG, KU Funding details: Deutsche Forschungsgemeinschaft, DFG Funding text 1: by the Deutsche Forschungsgemeinschaft (DFG, Grant KU Cited By :1 Export Date: 9 September 2021 Correspondence Address: Barth, D.; Institute of Physiology, Germany; email: dbarth@ukaachen.de Chemicals/CAS: phosphatidylinositol 4,5 bisphosphate, 94161-15-6; Phosphatidylinositol 4,5-Diphosphate; TRPM Cation Channels; TRPM2 protein, human Funding details: Deutsche Forschungsgemeinschaft, DFG, KU Funding text 1: by the Deutsche Forschungsgemeinschaft (DFG, Grant KU Cited By :1 Export Date: 10 September 2021 Correspondence Address: Barth, D.; Institute of Physiology, Germany; email: dbarth@ukaachen.de Chemicals/CAS: phosphatidylinositol 4,5 bisphosphate, 94161-15-6; Phosphatidylinositol 4,5-Diphosphate; TRPM Cation Channels; TRPM2 protein, human Funding details: Deutsche Forschungsgemeinschaft, DFG, KU Funding text 1: by the Deutsche Forschungsgemeinschaft (DFG, Grant KU Cited By :1 Export Date: 14 September 2021 Correspondence Address: Barth, D.; Institute of Physiology, Germany; email: dbarth@ukaachen.de Chemicals/CAS: phosphatidylinositol 4,5 bisphosphate, 94161-15-6; Phosphatidylinositol 4,5-Diphosphate; TRPM Cation Channels; TRPM2 protein, human Funding details: Deutsche Forschungsgemeinschaft, DFG, KU Funding text 1: by the Deutsche Forschungsgemeinschaft (DFG, Grant KU Cited By :1 Export Date: 15 September 2021 Correspondence Address: Barth, D.; Institute of Physiology, Germany; email: dbarth@ukaachen.de Chemicals/CAS: phosphatidylinositol 4,5 bisphosphate, 94161-15-6; Phosphatidylinositol 4,5-Diphosphate; TRPM Cation Channels; TRPM2 protein, human Funding details: Deutsche Forschungsgemeinschaft, DFG, KU Funding text 1: by the Deutsche Forschungsgemeinschaft (DFG, Grant KU AB - The human apoptosis channel TRPM2 is stimulated by intracellular ADR-ribose and cal-cium. Recent studies show pronounced species-specific activation mechanisms. Our aim was to an-alyse the functional effect of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), commonly referred to as PIP2, on different TRPM2 orthologues. Moreover, we wished to identify the interaction site between TRPM2 and PIP2. We demonstrate a crucial role of PIP2, in the activation of TRPM2 orthologues of man, zebrafish, and sea anemone. Utilizing inside-out patch clamp recordings of HEK-293 cells transfected with TRPM2, differential effects of PIP2 that were dependent on the species variant became apparent. While depletion of PIP2 via polylysine uniformly caused complete inactivation of TRPM2, restoration of channel activity by artificial PIP2 differed widely. Human TRPM2 was the least sensitive species variant, making it the most susceptible one for regulation by changes in intramembranous PIP2 content. Furthermore, mutations of highly conserved positively charged amino acid residues in the membrane interfacial cavity reduced the PIP2 sensitivity in all three TRPM2 orthologues to varying degrees. We conclude that the membrane interfacial cavity acts as a uniform PIP2 binding site of TRPM2, facilitating channel activation in the presence of ADPR and Ca2+ in a species-specific manner. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. LA - English DB - MTMT ER - TY - JOUR AU - Kuppusamy, Maniselvan AU - Ottolini, Matteo AU - Sonkusare, Swapnil K. TI - Role of TRP ion channels in cerebral circulation and neurovascular communication JF - NEUROSCIENCE LETTERS J2 - NEUROSCI LETT VL - 765 PY - 2021 PG - 10 SN - 0304-3940 DO - 10.1016/j.neulet.2021.136258 UR - https://m2.mtmt.hu/api/publication/32372253 ID - 32372253 N1 - Funding Agency and Grant Number: NIH [HL146914, HL142808] Funding text: This work was supported by grants from the NIH to SKS (HL146914 and HL142808) . AB - The dynamic regulation of blood flow is essential for meeting the high metabolic demands of the brain and maintaining brain function. Cerebral blood flow is regulated primarily by 1) the intrinsic mechanisms that determine vascular contractility and 2) signals from neurons and astrocytes that alter vascular contractility. Stimuli from neurons and astrocytes can also initiate a signaling cascade in the brain capillary endothelium to increase regional blood flow. Recent studies provide evidence that TRP channels in endothelial cells, smooth muscle cells, neurons, astrocytes, and perivascular nerves control cerebrovascular contractility and cerebral blood flow. TRP channels exert their functional effects either through cell membrane depolarization or by serving as a Ca2+ influx pathway. Endothelial cells and astrocytes also maintain the integrity of the blood-brain barrier. Both endothelial cells and astrocytes express TRP channels, and an increase in endothelial TRP channel activity has been linked with a disrupted endothelial barrier function. Therefore, TRP channels can play a potentially important role in regulating blood-brain barrier integrity. Here, we review the regulation of cerebrovascular contractility by TRP channels under healthy and disease conditions and their potential roles in maintaining blood-brain barrier function. 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 - 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 - 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 - Elena Lopez-Romero, Ana AU - Hernandez-Araiza, Ileana AU - Torres-Quiroz, Francisco AU - Tovar-Y-Romo, Luis B. AU - Islas, Leon D. AU - Rosenbaum, Tamara TI - TRP ion channels: Proteins with conformational flexibility JF - CHANNELS J2 - CHANNELS VL - 13 PY - 2019 IS - 1 SP - 207 EP - 226 PG - 20 SN - 1933-6950 DO - 10.1080/19336950.2019.1626793 UR - https://m2.mtmt.hu/api/publication/30746777 ID - 30746777 N1 - Funding Agency and Grant Number: Consejo Nacional de Ciencia y TecnologiaConsejo Nacional de Ciencia y Tecnologia (CONACyT) [A1-S-8760]; Direccion General de Asuntos del Personal Academico, Universidad Nacional Autonoma de MexicoUniversidad Nacional Autonoma de Mexico [IN200717] Funding text: This work was supported by the Consejo Nacional de Ciencia y Tecnologia [A1-S-8760]; Direccion General de Asuntos del Personal Academico, Universidad Nacional Autonoma de Mexico [IN200717]; Export Date: 7 January 2020 Correspondence Address: Rosenbaum, T.; Departamento de Neurociencia Cognitiva, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de MéxicoMexico; email: trosenba@ifc.unam.mx Export Date: 8 January 2020 Correspondence Address: Rosenbaum, T.; Departamento de Neurociencia Cognitiva, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de MéxicoMexico; email: trosenba@ifc.unam.mx Departamento de Neurociencia Cognitiva, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico, Mexico Departamento de Bioquímica y Biología Estructural, División Investigación Básica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico Departamento de Neuropatología Molecular, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico Cited By :3 Export Date: 26 March 2020 Correspondence Address: Rosenbaum, T.; Departamento de Neurociencia Cognitiva, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de MéxicoMexico; email: trosenba@ifc.unam.mx Departamento de Neurociencia Cognitiva, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico, Mexico Departamento de Bioquímica y Biología Estructural, División Investigación Básica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico Departamento de Neuropatología Molecular, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico Cited By :4 Export Date: 2 February 2021 Correspondence Address: Rosenbaum, T.; Departamento de Neurociencia Cognitiva, Mexico; email: trosenba@ifc.unam.mx AB - Ion channels display conformational changes in response to binding of their agonists and antagonists. The study of the relationships between the structure and the function of these proteins has witnessed considerable advances in the last two decades using a combination of techniques, which include electrophysiology, optical approaches (i.e. patch clamp fluorometry, incorporation of non-canonic amino acids, etc.), molecular biology (mutations in different regions of ion channels to determine their role in function) and those that have permitted the resolution of their structures in detail (X-ray crystallography and cryo-electron microscopy). The possibility of making correlations among structural components and functional traits in ion channels has allowed for more refined conclusions on how these proteins work at the molecular level. With the cloning and description of the family of Transient Receptor Potential (TRP) channels, our understanding of several sensory-related processes has also greatly moved forward. The response of these proteins to several agonists, their regulation by signaling pathways as well as by protein-protein and lipid-protein interactions and, in some cases, their biophysical characteristics have been studied thoroughly and, recently, with the resolution of their structures, the field has experienced a new boom. This review article focuses on the conformational changes in the pores, concentrating on some members of the TRP family of ion channels (TRPV and TRPA subfamilies) that result in changes in their single-channel conductances, a phenomenon that may lead to fine-tuning the electrical response to a given agonist in a cell. 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 - Kühn, Frank J P AU - Watt, Joanna M AU - Potter, Barry V L AU - Lückhoff, Andreas TI - Different substrate specificities of the two ADPR binding sites in TRPM2 channels of Nematostella vectensis and the role of IDPR. JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 9 PY - 2019 IS - 1 SN - 2045-2322 DO - 10.1038/s41598-019-41531-4 UR - https://m2.mtmt.hu/api/publication/30628107 ID - 30628107 N1 - Funding Agency and Grant Number: Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [KU 2271/4-2]; [101010] Funding text: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). BVLP is a Wellcome Trust Senior Investigator (Grant 101010). 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 Institute of Physiology, Medical Faculty, RWTH Aachen, Aachen, D52057, Germany 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, Claverton Down, Bath, BA2 7AY, United Kingdom Cited By :7 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). BVLP is a Wellcome Trust Senior Investigator (Grant 101010). AB - NvTRPM2 (Nematostella vectensis Transient Receptor Potential Melastatin 2), the species variant of the human apoptosis-related cation channel hTRPM2, is gated by ADP-ribose (ADPR) independently of the C-terminal NUDT9H domain that mediates ADPR-directed gating in hTRPM2. The decisive binding site in NvTRPM2 is likely to be identical with the N-terminal ADPR binding pocket in zebra fish DrTRPM2. Our aim was a characterization of this binding site in NvTRPM2 with respect to its substrate specificity, in comparison to the classical ADPR interaction site within NUDT9H that is highly homologous in hTRPM2 and NvTRPM2, although only in NvTRPM2, catalytic (ADPRase) activity is conserved. With various ADPR analogues, key differences of the two sites were identified. Particularly, two reported antagonists on hTRPM2 were agonists on NvTRPM2. Moreover, IDP-ribose (IDPR) induced currents both in hTRPM2 and NvTRPM2 but not in NvTRPM2 mutants in which NUDT9H was absent. Thus, IDPR acts on NUDT9H rather than N-terminally, revealing a regulatory function of NUDT9H in NvTRPM2 opposed to that in hTRPM2. We propose that IDPR competitively inhibits the ADPRase function of NUDT9H and evokes ADPR accumulation. The findings provide important insights into the structure-function relationship of NvTRPM2 and will allow further characterization of the novel ADPR interaction site. 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 - 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 - 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 - Boonen, B AU - Startek, JB AU - Talavera, K ED - Krautwurst, Dietmar TI - Chemical activation of sensory TRP channels T2 - Taste and Smell PB - Springer Netherlands CY - Cham SN - 9783319489278 T3 - Topics in Medicinal Chemistry, ISSN 1862-2461 ; 23. PY - 2017 SP - 73 EP - 114 PG - 42 DO - 10.1007/7355_2015_98 UR - https://m2.mtmt.hu/api/publication/26355293 ID - 26355293 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 - Li, Jun AU - Gao, Yunling AU - Bao, Xianying AU - Li, Fengna AU - Yao, Wei AU - Feng, Zemeng AU - Yin, Yulong TI - TRPM2: a potential drug target to retard oxidative stress JF - FRONTIERS IN BIOSCIENCE-LANDMARK J2 - FRONT BIOSCI-LANDMARK VL - 22 PY - 2017 SP - 1427 EP - 1438 PG - 12 SN - 2768-6701 DO - 10.2741/4551 UR - https://m2.mtmt.hu/api/publication/26578581 ID - 26578581 N1 - Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control, Waste Utilization in Livestock and Poultry Production, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha, Hunan, 410125, China Xiangyang Central Hospital, Affliated Hospital of Hubei University of Arts and Science, Xiangyang441021, China College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China University of Chinese Academy of Sciences, Beijing, 100049, China Department of Cardiology, Tianjin Medical University General Hospital, Tianjin Medial University, Tianjin, 300052, China Hunan Co-Innovation Center of Animal Production Safety, CICAPS, Changsha, 410128, China Cited By :8 Export Date: 20 September 2019 Correspondence Address: Feng, Z.Mapoling of Changsha City, China; email: zemengfeng2006@163.com Funding Agency and Grant Number: Chinese Academy of Science STS Project [KFJ-SW-STS-173]; National "948" Project from the Ministry of Agriculture of China [2015Z74]; international Partnership Program of Chinese Academy of Sciences grant [161343KYSB20160008]; Science and Technology Development Fund Project of Tianjin [20130138] Funding text: Jun Li and Yunling Gao contributed equally to this work. Thank Dr. Yun Su for her figures drawing work. This research was jointly supported by the Chinese Academy of Science STS Project (KFJ-SW-STS-173), the National "948" Project from the Ministry of Agriculture of China (2015Z74), the international Partnership Program of Chinese Academy of Sciences grant (161343KYSB20160008), and Science and Technology Development Fund Project of Tianjin (20130138). Export Date: 7 January 2020 Correspondence Address: Feng, Z.Mapoling of Changsha City, China; email: zemengfeng2006@163.com LA - English DB - MTMT ER - TY - THES AU - Pahnke, Katharina TI - Synthese funktionalisierter Zuckernucleotide und deren Anwendbarkeit als biologische Tools PY - 2017 UR - https://m2.mtmt.hu/api/publication/30638059 ID - 30638059 LA - German DB - MTMT ER - TY - GEN AU - Šulcová, Dominika TI - The role of spinal TRPV1 receptors in nociceptive signalling and the modulatory effect of chemokine CCL2 and µ-opioid receptor agonists PY - 2017 UR - https://m2.mtmt.hu/api/publication/30638060 ID - 30638060 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 - TY - JOUR AU - Chibber, Sandesh AU - Alexiou, Athanasios AU - Alama, Mohammed Nabil AU - Emilio, Barreto George AU - Aliev, Gjumrakch AU - Ashraf, Ghulam Mohammad TI - A Synopsis on the Linkage Between Age-Related Dementias and Vascular Disorders JF - CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS J2 - CNS NEUROL DISORD-DR VL - 15 PY - 2016 IS - 2 SP - 250 EP - 258 PG - 9 SN - 1871-5273 DO - 10.2174/1871527315666160202121809 UR - https://m2.mtmt.hu/api/publication/25784873 ID - 25784873 N1 - Funding Agency and Grant Number: GALLY International Biomedical Research Consulting LLC, San Antonio, TX USA Funding text: The authors are grateful to the Deanship of Scientific Research (DSR) and King Fahd Medical Research Center (KFMRC), King Abdulaziz University (Jeddah, Saudi Arabia) for the facilities provided. Gjumrakch Aliev was supported by the GALLY International Biomedical Research Consulting LLC, San Antonio, TX USA. Part of the experimental work was performed using the equipment of Center for collective use of IPAC RAS (Agreement No 14.621.21.0008, ID RFMEFI62114X0008). Export Date: 7 January 2020 Correspondence Address: Ashraf, G.M.; King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Saudi Arabia; email: gashraf@kau.edu.sa LA - English DB - MTMT ER - TY - JOUR AU - Iordanov, Iordan AU - Mihályi, Csaba AU - Tóth, Balázs AU - Csanády, László TI - The proposed channel-enzyme transient receptor potential melastatin 2 does not possess ADP ribose hydrolase activity JF - ELIFE J2 - ELIFE VL - 5 PY - 2016 PG - 20 SN - 2050-084X DO - 10.7554/eLife.17600 UR - https://m2.mtmt.hu/api/publication/3105008 ID - 3105008 N1 - Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary MTA-SE Ion Channel Research Group, Semmelweis University, Budapest, Hungary Cited By :17 Export Date: 20 September 2019 Correspondence Address: Csanády, L.; Department of Medical Biochemistry, Semmelweis UniversityHungary; email: csanady.laszlo@med.semmelweis-univ.hu Funding Agency and Grant Number: Howard Hughes Medical Institute International Early Career Scientist [55007416]; Magyar Tudomanyos Akademia Lendulet [LP2012-39/2012] Funding text: Howard Hughes Medical Institute International Early Career Scientist grant, 55007416 Laszlo Csanady; Magyar Tudomanyos Akademia Lendulet grant, LP2012-39/2012 Laszlo Csanady Export Date: 7 January 2020 Correspondence Address: Csanády, L.; Department of Medical Biochemistry, Semmelweis UniversityHungary; email: csanady.laszlo@med.semmelweis-univ.hu LA - English DB - MTMT ER - TY - JOUR AU - Kuehn, Frank J P AU - Kuehn, Cornelia AU - Winking, Mathis AU - Hoffmann, Daniel C AU - Lueckhoff, Andreas TI - ADP-Ribose Activates the TRPM2 Channel from the Sea Anemone Nematostella vectensis Independently of the NUDT9H Domain JF - PLOS ONE J2 - PLOS ONE VL - 11 PY - 2016 IS - 6 PG - 21 SN - 1932-6203 DO - 10.1371/journal.pone.0158060 UR - https://m2.mtmt.hu/api/publication/26029746 ID - 26029746 N1 - Cited By :8 Export Date: 20 September 2019 CODEN: POLNC Funding Agency and Grant Number: Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [KU 2271/4-1] Funding text: The study was supported by the Deutsche Forschungsgemeinschaft (www.dfg.de), grant number: KU 2271/4-1 to FK. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Export Date: 7 January 2020 CODEN: POLNC LA - English DB - MTMT ER - TY - JOUR AU - Li, F-Y AU - Wong, R AU - Turlova, E AU - Sun, H-S TI - Pathological role of transient receptor potential melastatin member 2 channel in neurodegenerative diseases and Alzheimer disease JF - CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY / ZHONG GUO YAO LI XUE YU DU LI XUE ZA ZHI J2 - CHINESE J PHARM TOXICOL VL - 30 PY - 2016 IS - 6 SP - 656 EP - 666 PG - 11 SN - 1000-3002 DO - 10.3867/j.issn.1000-3002.2016.06.005 UR - https://m2.mtmt.hu/api/publication/26178279 ID - 26178279 N1 - Export Date: 7 January 2020 CODEN: ZYYZE Correspondence Address: Sun, H.-S.; Department of Physiology, University of TorontoCanada; email: hss.sun@utoronto.ca LA - English DB - MTMT ER - TY - JOUR AU - Ogawa, Nozomi AU - Kurokawa, Tatsuki AU - Mori, Yasuo TI - Sensing of redox status by TRP channels JF - CELL CALCIUM J2 - CELL CALCIUM VL - 60 PY - 2016 IS - 2 SP - 115 EP - 122 PG - 8 SN - 0143-4160 DO - 10.1016/j.ceca.2016.02.009 UR - https://m2.mtmt.hu/api/publication/26170511 ID - 26170511 N1 - Funding Agency and Grant Number: Ministry of Education, Culture, Sports, Science and Technology, JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [26111004]; Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [24249017] Funding text: This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas "Oxygen biology: a new criterion for integrated understanding of life" [26111004] of The Ministry of Education, Culture, Sports, Science and Technology, Japan; and a Grant-in-Aid for Scientific Research (A) [24249017] of Japan Society for the Promotion of Science. Export Date: 7 January 2020 CODEN: CECAD Correspondence Address: Mori, Y.; Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto UniversityJapan; email: mori@sbchem.kyoto-u.ac.jp Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, 615-8510, Japan Laboratory of Environmental Systems Biology, Department of Technology and Ecology, Hall of Global Environmental Studies, Kyoto University, Kyoto, 615-8510, Japan Cited By :30 Export Date: 29 January 2020 CODEN: CECAD Correspondence Address: Mori, Y.; Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto UniversityJapan; email: mori@sbchem.kyoto-u.ac.jp LA - English DB - MTMT ER - TY - JOUR AU - Lambie, Eric J AU - Bruce, Robert D III AU - Zielich, Jeffrey AU - Yuen, Sonia N TI - Novel Alleles of gon-2, a C-elegans Ortholog of Mammalian TRPM6 and TRPM7, Obtained by Genetic Reversion Screens JF - PLOS ONE J2 - PLOS ONE VL - 10 PY - 2015 IS - 11 PG - 16 SN - 1932-6203 DO - 10.1371/journal.pone.0143445 UR - https://m2.mtmt.hu/api/publication/25361600 ID - 25361600 N1 - Funding Agency and Grant Number: National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01GM49785] Funding text: EJL was the recipient of National Institutes of Health grant R01GM49785. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Export Date: 7 January 2020 CODEN: POLNC LA - English DB - MTMT ER - TY - JOUR AU - Rosenbaum, Tamara TI - Activators of TRPM2: Getting it right JF - JOURNAL OF GENERAL PHYSIOLOGY J2 - J GEN PHYSIOL VL - 145 PY - 2015 IS - 6 SP - 485 EP - 487 PG - 3 SN - 0022-1295 DO - 10.1085/jgp.201511405 UR - https://m2.mtmt.hu/api/publication/25361599 ID - 25361599 N1 - Export Date: 7 January 2020 CODEN: JGPLA Correspondence Address: Rosenbaum, T.; Departamento de Neurodesarrollo y Fisiología, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de MéxicoMexico; email: trosenba@ifc.unam.mx LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Balázs AU - Iordanov, Iordan AU - Csanády, László TI - Ruling out pyridine dinucleotides as true TRPM2 channel activators reveals novel direct agonist ADP-ribose-2'-phosphate JF - JOURNAL OF GENERAL PHYSIOLOGY J2 - J GEN PHYSIOL VL - 145 PY - 2015 IS - 5 SP - 419 EP - 430 PG - 12 SN - 0022-1295 DO - 10.1085/jgp.201511377 UR - https://m2.mtmt.hu/api/publication/2949645 ID - 2949645 N1 - Funding Agency and Grant Number: International Early Career Scientist grant from the Howard Hughes Medical InstituteHoward Hughes Medical Institute; MTA Lendulet grant [LP2012-39/2012] Funding text: This work is supported by an International Early Career Scientist grant from the Howard Hughes Medical Institute to L. Csanady, and MTA Lendulet grant LP2012-39/2012. Export Date: 7 January 2020 CODEN: JGPLA Correspondence Address: Csanády, L.; Department of Medical Biochemistry, Semmelweis UniversityHungary; email: csanay.laszlo@med.semmelweis-univ.hu AB - Transient receptor potential melastatin 2 (TRPM2), a Ca(2+)-permeable cation channel implicated in postischemic neuronal cell death, leukocyte activation, and insulin secretion, is activated by intracellular ADP ribose (ADPR). In addition, the pyridine dinucleotides nicotinamide-adenine-dinucleotide (NAD), nicotinic acid-adenine-dinucleotide (NAAD), and NAAD-2'-phosphate (NAADP) have been shown to activate TRPM2, or to enhance its activation by ADPR, when dialyzed into cells. The precise subset of nucleotides that act directly on the TRPM2 protein, however, is unknown. Here, we use a heterologously expressed, affinity-purified-specific ADPR hydrolase to purify commercial preparations of pyridine dinucleotides from substantial contaminations by ADPR or ADPR-2'-phosphate (ADPRP). Direct application of purified NAD, NAAD, or NAADP to the cytosolic face of TRPM2 channels in inside-out patches demonstrated that none of them stimulates gating, or affects channel activation by ADPR, indicating that none of these dinucleotides directly binds to TRPM2. Instead, our experiments identify for the first time ADPRP as a true direct TRPM2 agonist of potential biological interest. LA - English DB - MTMT ER -