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 - TY - JOUR AU - Csanády, László AU - Törőcsik, Beáta TI - Catalyst-like Modulation of Transitions States for CFTR Channel Opening and Closing: New Stimulation Strategy Exploits Nonequilibrium Gating JF - JOURNAL OF GENERAL PHYSIOLOGY J2 - J GEN PHYSIOL VL - 143 PY - 2014 IS - 2 SP - 269 EP - 287 PG - 19 SN - 0022-1295 DO - 10.1085/jgp.201311089 UR - https://m2.mtmt.hu/api/publication/2496247 ID - 2496247 LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Balázs AU - Iordanov, Iordan AU - Csanády, László TI - Putative chanzyme activity of TRPM2 cation channel is unrelated to pore gating JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA J2 - P NATL ACAD SCI USA VL - 111 PY - 2014 IS - 47 SP - 16949 EP - 16954 PG - 6 SN - 0027-8424 DO - 10.1073/pnas.1412449111 UR - https://m2.mtmt.hu/api/publication/2762109 ID - 2762109 N1 - Funding Agency and Grant Number: Howard Hughes Medical InstituteHoward Hughes Medical Institute; MTA Lendulet Grant [LP2012-39/2012] Funding text: This work was supported by an International Early Career Scientist grant from the Howard Hughes Medical Institute (to L. C.) and MTA Lendulet Grant LP2012-39/2012. Department of Medical Biochemistry, Semmelweis University, Budapest, H-1094, Hungary Magyar Tudományos Akadémia - Semmelweis Egyetem Lendület (MTA-SE), Semmelweis University, Budapest, H-1094, Hungary Cited By :25 Export Date: 7 January 2020 CODEN: PNASA Correspondence Address: Csanády, L.; Department of Medical Biochemistry, Semmelweis UniversityHungary LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Balázs AU - Csanády, László TI - Pore collapse underlies irreversible inactivation of TRPM2 cation channel currents. JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA J2 - P NATL ACAD SCI USA VL - 109 PY - 2012 IS - 33 SP - 13440 EP - 13445 PG - 6 SN - 0027-8424 DO - 10.1073/pnas.1204702109 UR - https://m2.mtmt.hu/api/publication/2041974 ID - 2041974 N1 - Funding Agency and Grant Number: Orszagos Tudomanyos Kutatasi Alapprogramok Grant [F 68143]; Howard Hughes Medical InstituteHoward Hughes Medical Institute Funding text: We thank Dorottya Mayer for oocyte isolation and injection; Tibor Rohacs for the TRPM8 clone, for PIP2, and for much valuable advice; and David Gadsby for discussions. L. C. is a Bolyai Research Fellow of the Hungarian Academy of Sciences. Support for this work was provided by Orszagos Tudomanyos Kutatasi Alapprogramok Grant F 68143 (to L. C.) and an International Early Career Scientist grant from the Howard Hughes Medical Institute (to L.C.). Cited By :33 Export Date: 7 January 2020 CODEN: PNASA Correspondence Address: Csanády, L.; Department of Medical Biochemistry, Semmelweis University, Budapest H-1094, Hungary; email: csanady.laszlo@med.semmelweis-univ.hu AB - The Ca(2+)-permeable cation channel transient receptor potential melastatin 2 (TRPM2) plays a key role in pathogen-evoked phagocyte activation, postischemic neuronal apoptosis, and glucose-evoked insulin secretion, by linking these cellular responses to oxidative stress. TRPM2 channels are coactivated by binding of intracellular ADP ribose and Ca(2+) to distinct cytosolically accessible sites on the channels. These ligands likely regulate the activation gate, conserved in the voltage-gated cation channel superfamily, that comprises a helix bundle formed by the intracellular ends of transmembrane helix six of each subunit. For several K(+) and TRPM family channels, activation gate opening requires the presence of phosphatidylinositol-bisphosphate (PIP(2)) in the inner membrane leaflet. Most TRPM family channels inactivate upon prolonged stimulation in inside-out patches; this "rundown" is due to PIP(2) depletion. TRPM2 currents also run down within minutes, but the molecular mechanism of this process is unknown. Here we report that high-affinity PIP(2) binding regulates Ca(2+) sensitivity of TRPM2 activation. Nevertheless, TRPM2 inactivation is not due to PIP(2) depletion; rather, it is state dependent, sensitive to permeating ions, and can be completely prevented by mutations in the extracellular selectivity filter. Introduction of two negative charges plus a single-residue insertion, to mimic the filter sequence of TRPM5, results in TRPM2 channels that maintain unabated maximal activity for over 1 h, and display altered permeation properties but intact ADP ribose/Ca(2+)-dependent gating. Thus, upon prolonged stimulation, the TRPM2 selectivity filter undergoes a conformational change reminiscent of that accompanying C-type inactivation of voltage-gated K(+) channels. The noninactivating TRPM2 variant will be invaluable for gating studies. LA - English DB - MTMT ER - TY - JOUR AU - Csanády, László AU - Vergani, P AU - Gadsby, DC TI - Strict coupling between CFTR's catalytic cycle and gating of its Cl- ion pore revealed by distributions of open channel burst durations JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA J2 - P NATL ACAD SCI USA VL - 107 PY - 2010 IS - 3 SP - 1241 EP - 1246 PG - 6 SN - 0027-8424 DO - 10.1073/pnas.0911061107 UR - https://m2.mtmt.hu/api/publication/1493081 ID - 1493081 LA - English DB - MTMT ER - TY - JOUR AU - Csanády, László TI - Application of rate-equilibrium free energy relationship analysis to nonequilibrium ion channel gating mechanisms JF - JOURNAL OF GENERAL PHYSIOLOGY J2 - J GEN PHYSIOL VL - 134 PY - 2009 IS - 2 SP - 129 EP - 136 PG - 8 SN - 0022-1295 DO - 10.1085/jgp.200910268 UR - https://m2.mtmt.hu/api/publication/1493082 ID - 1493082 N1 - Cited By :8 Export Date: 9 March 2022 CODEN: JGPLA Correspondence Address: Csanády, L.; Department of Medical Biochemistry, , Budapest H-1094, Hungary; email: laszlo.csanady@-eok.sote.hu Chemicals/CAS: adenosine triphosphate, 15237-44-2, 56-65-5, 987-65-5; Ion Channels Funding details: Fogarty International Center, FIC, R03TW007829 Funding details: National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK, R01DK051767 LA - English DB - MTMT ER - TY - JOUR AU - Csanády, László AU - Törőcsik, Beáta TI - Four Ca2+ Ions Activate TRPM2 Channels by Binding in Deep Crevices near the Pore but Intracellularly of the Gate JF - JOURNAL OF GENERAL PHYSIOLOGY J2 - J GEN PHYSIOL VL - 133 PY - 2009 IS - 2 SP - 189 EP - 203 PG - 15 SN - 0022-1295 DO - 10.1085/jgp.200810109 UR - https://m2.mtmt.hu/api/publication/1502468 ID - 1502468 LA - English DB - MTMT ER - TY - JOUR AU - Gadsby, DC AU - Vergani, P AU - Csanády, László TI - The ABC protein turned chloride channel whose failure causes cystic fibrosis JF - NATURE J2 - NATURE VL - 440 PY - 2006 IS - 7083 SP - 477 EP - 483 PG - 7 SN - 0028-0836 DO - 10.1038/nature04712 UR - https://m2.mtmt.hu/api/publication/1493088 ID - 1493088 N1 - Funding Agency and Grant Number: Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [G0501200] Funding Source: Medline; NIDDK NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01 DK051767, R01 DK051767-10] Funding Source: Medline; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01DK051767] Funding Source: NIH RePORTER Cited By :498 Export Date: 31 August 2021 CODEN: NATUA Correspondence Address: Gadsby, D.C.; Laboratory of Cardiac/Membrane Physiology, Rockefeller University, New York, NY 10021, United States; email: gadsby@rockefeller.edu LA - English DB - MTMT ER -