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dc.contributor.author
Aprile-Garcia, Fernando
dc.contributor.author
Metzger, Michael W.
dc.contributor.author
Paez-Pereda, Marcelo
dc.contributor.author
Stadler, Herbert
dc.contributor.author
Acuña, Matías
dc.contributor.author
Liberman, Ana C.
dc.contributor.author
Senin, Sergio A.
dc.contributor.author
Gerez, Juan
dc.contributor.author
Hoijman, Esteban
dc.contributor.author
Refojo, Damian
dc.contributor.author
Mitkoovski, Mišo
dc.contributor.author
Panhuysen, Markus
dc.contributor.author
Stühmer, Walter
dc.contributor.author
Holsboer, Florian
dc.contributor.author
Deussing, Jan M.
dc.contributor.author
Arzt, Eduardo
dc.date.accessioned
2018-11-01T15:20:46Z
dc.date.available
2017-06-12T18:07:14Z
dc.date.available
2018-11-01T15:20:46Z
dc.date.issued
2016-03-17
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0151862
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/125492
dc.identifier.doi
10.3929/ethz-b-000125492
dc.description.abstract
The P2X7 receptor is a member of the P2X family of ligand-gated ion channels. A single-nucleotide polymorphism leading to a glutamine (Gln) by arginine (Arg) substitution at codon 460 of the purinergic P2X7 receptor (P2X7R) has been associated with mood disorders. No change in function (loss or gain) has been described for this SNP so far. Here we show that although the P2X7R-Gln460Arg variant per se is not compromised in its function, co-expression of wild-type P2X7R with P2X7R-Gln460Arg impairs receptor function with respect to calcium influx, channel currents and intracellular signaling in vitro. Moreover, co-immunoprecipitation and FRET studies show that the P2X7R-Gln460Arg variant physically interacts with P2X7R-WT. Specific silencing of either the normal or polymorphic variant rescues the heterozygous loss of function phenotype and restores normal function. The described loss of function due to co-expression, unique for mutations in the P2RX7 gene so far, explains the mechanism by which the P2X7R-Gln460Arg variant affects the normal function of the channel and may represent a mechanism of action for other mutations.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Co-Expression of Wild-Type P2X7R with Gln460Arg Variant Alters Receptor Function
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
PLoS ONE
ethz.journal.volume
11
en_US
ethz.journal.issue
3
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e0151862
en_US
ethz.size
16 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.nebis
006206116
ethz.publication.place
San Francisco, CA, USA
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02515 - Laboratorium für Physikalische Chemie / Laboratory of Physical Chemistry::03782 - Riek, Roland / Riek, Roland
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02515 - Laboratorium für Physikalische Chemie / Laboratory of Physical Chemistry::03782 - Riek, Roland / Riek, Roland
ethz.date.deposited
2017-06-12T18:07:23Z
ethz.source
ECIT
ethz.identifier.importid
imp59365511079dc12903
ethz.ecitpid
pub:188097
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-20T18:53:34Z
ethz.rosetta.lastUpdated
2018-11-01T15:21:05Z
ethz.rosetta.versionExported
true
ethz.COinS
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