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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
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Enzyme activity and selectivity filter stability of ancient TRPM2 channels were simultaneously lost in early vertebrates
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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.
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" mtid="10052053"> <a href="/gui2/?type=authors&mode=browse&sel=10052053" target="_blank">Iordanov, Iordan</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10024493"> <a href="/gui2/?type=authors&mode=browse&sel=10024493" target="_blank">Tóth, Balázs<sup>*</sup></a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10020191"> <a href="/gui2/?type=authors&mode=browse&sel=10020191" target="_blank">Szollosi, Andras</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10015499"> <a href="/gui2/?type=authors&mode=browse&sel=10015499" target="_blank">Csanády, László ✉</a> </span> <span class="author-type"> </span> </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;30637149" mtid="30637149" target="_blank">Enzyme activity and selectivity filter stability of ancient TRPM2 channels were simultaneously lost in early vertebrates</a></div> <div class="pub-info"> <span class="journal-title">ELIFE</span> <span class="journal-volume">8</span> : <span class="journal-issue">2019</span> <span class="page"> Paper: e44556 , 23 p. </span> <span class="year">(2019)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.7554/eLife.44556" target="_blank" href="https://doi.org/10.7554/eLife.44556"> DOI </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:black" title="98903" target="_blank" href="http://real.mtak.hu/98903"> REAL </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="7628" target="_blank" href="https://repo.lib.semmelweis.hu/handle/123456789/7628"> SE Repozitórium </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000464410300001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000464410300001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85064725932" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85064725932"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="30938679" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=30938679&dopt=Abstract"> PubMed </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="short-pub-mtid"> Közlemény:30637149 </span> <span class="status-holder"><span class="status-data status-VALIDATED"> Egyeztetett </span></span> <span class="pub-core">Forrás Idéző </span> <span class="pub-type">Folyóiratcikk (Szakcikk ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Tudományos</span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 17</span> | Független: 12 | Függő: 5 | Nem jelölt: 0 | WoS jelölt: 17 | Scopus jelölt: 16 | WoS/Scopus jelölt: 17 | DOI jelölt: 17 </div> </div> </div> </div><div class="JournalArticle Publication long-list">
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<div class="autype autype0"> <span class="author-name" mtid="10052053"><a
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<span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Orvosi Biokémiai Intézet; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Orvosi Biokémiai Intézet">OBI</span>/MTA-SE Lendület Ioncsatorna Kutatócsoport</span>
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<span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Orvosi Biokémiai Intézet; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Orvosi Biokémiai Intézet">OBI</span>/MTA-SE Lendület Ioncsatorna Kutatócsoport</span>
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<span class="author-name" mtid="10015499"><a
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<span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Orvosi Biokémiai Intézet; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Orvosi Biokémiai Intézet">OBI</span>/MTA-SE Lendület Ioncsatorna Kutatócsoport</span>
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<div class="title"><a href="/gui2/?mode=browse¶ms=publication;30637149" target="_blank">Enzyme activity and selectivity filter stability of ancient TRPM2 channels were simultaneously lost in early vertebrates</a></div> <div> <span class="journal-title">ELIFE</span>
<span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/2050-084X">2050-084X</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/2050-084X">2050-084X</a>)</span>:
<span class="journal-volume">8</span> <span class="journal-issue">2019</span>
<span class="page">
Paper e44556.
23 p.
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<span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 17</span>
| Független: 12
| Függő: 5
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<div class="lastModified">Utolsó módosítás: 2021.04.07. 11:55 xBökönyi Zita (INAKTÍV_SE_AOK_OBI_Admin5_BZ, admin)
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<pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: 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 LP201...</pre>
</div></div>