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 - Tóth, Balázs AU - Csanády, László TI - Identification of Direct and Indirect Effectors of the Transient Receptor Potential Melastatin 2 (TRPM2) Cation Channel JF - JOURNAL OF BIOLOGICAL CHEMISTRY J2 - J BIOL CHEM VL - 285 PY - 2010 IS - 39 SP - 30091 EP - 30102 PG - 12 SN - 0021-9258 DO - 10.1074/jbc.M109.066464 UR - https://m2.mtmt.hu/api/publication/1493078 ID - 1493078 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 - Balla, András AU - Balla, Tamás TI - Phosphatidylinositol 4-kinases: old enzymes with emerging functions JF - TRENDS IN CELL BIOLOGY J2 - TRENDS CELL BIOL VL - 16 PY - 2006 IS - 7 SP - 351 EP - 361 PG - 11 SN - 0962-8924 DO - 10.1016/j.tcb.2006.05.003 UR - https://m2.mtmt.hu/api/publication/1134169 ID - 1134169 N1 - Megjegyzés-20429105 Cited By (since 1996): 24 AB - Phosphoinositides account for only a tiny fraction of cellular phospholipids but are extremely important in the regulation of the recruitment and activity of many signaling proteins in cellular membranes. Phosphatidylinositol (PtdIns) 4-kinases generate PtdIns 4-phosphate, the precursor of important regulatory phosphoinositides but also an emerging regulatory molecule in its own right. The four mammalian PtdIns 4-kinases regulate a diverse array of signaling events, as well as vesicular trafficking and lipid transport, but the mechanisms by which their lipid product PtdIns 4-phosphate controls these processes is only beginning to unfold. Š 2006 Elsevier Ltd. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Csanády, László AU - Ádám, Veronika TI - Antagonistic regulation of native Ca2+- and ATP-sensitive cation channels in brain capillaries by nucleotides and decavanadate JF - JOURNAL OF GENERAL PHYSIOLOGY J2 - J GEN PHYSIOL VL - 123 PY - 2004 IS - 6 SP - 743 EP - 757 PG - 15 SN - 0022-1295 DO - 10.1085/jgp.200309008 UR - https://m2.mtmt.hu/api/publication/1030898 ID - 1030898 LA - English DB - MTMT ER - TY - JOUR AU - Csanády, László AU - Ádám, Veronika TI - Ca2+- and voltage-dependent gating of Ca2+- and ATP-sensitive cationic channels in brain capillary endothelium JF - BIOPHYSICAL JOURNAL J2 - BIOPHYS J VL - 85 PY - 2003 IS - 1 SP - 313 EP - 327 PG - 15 SN - 0006-3495 DO - 10.1016/S0006-3495(03)74476-2 UR - https://m2.mtmt.hu/api/publication/1030904 ID - 1030904 LA - English DB - MTMT ER -