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  - 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  -