Autoinactivation of the Stargazin–AMPA Receptor Complex: Subunit-Dependency and Independence from Physical Dissociation

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dc.contributor University of Helsinki, Medicum en
dc.contributor University of Helsinki, Medicum en
dc.contributor University of Helsinki, Biosciences en
dc.contributor University of Helsinki, Biosciences en
dc.contributor.author Semenov, Artur
dc.contributor.author Möykkynen, Tommi Petteri
dc.contributor.author Korpi, Esa Risto
dc.contributor.author Coleman, Sarah Kate
dc.contributor.author Keinänen, Kari
dc.date.accessioned 2013-11-22T12:34:01Z
dc.date.available 2013-11-22T12:34:01Z
dc.date.issued 2012
dc.identifier.citation Semenov , A , Möykkynen , T P , Korpi , E R , Coleman , S K & Keinänen , K 2012 , ' Autoinactivation of the Stargazin–AMPA Receptor Complex: Subunit-Dependency and Independence from Physical Dissociation ' , PLoS One , vol. 7 , no. 11 , pp. e49282 . https://doi.org/10.1371/journal.pone.0049282 en
dc.identifier.issn 1932-6203
dc.identifier.other PURE: 25522026
dc.identifier.other PURE UUID: 12cecd6f-ce6b-4cc2-875b-50425f3acefc
dc.identifier.other WOS: 000311151900116
dc.identifier.other Scopus: 84869139685
dc.identifier.other ORCID: /0000-0003-0683-4009/work/29948620
dc.identifier.other ORCID: /0000-0001-5759-5533/work/29922392
dc.identifier.uri http://hdl.handle.net/10138/42084
dc.description.abstract are modulated by transmembrane accessory proteins. Stargazin, the prototypical accessory protein, decreases desensitization and increases agonist potency at AMPA receptors. Furthermore, in the presence of stargazin, the steadystate responses of AMPA receptors show a gradual decline at higher glutamate concentrations. This ‘‘autoinactivation’’ has been assigned to physical dissociation of the stargazin-AMPA receptor complex and suggested to serve as a protective mechanism against overactivation. Here, we analyzed autoinactivation of GluA1–A4 AMPA receptors (all flip isoform) expressed in the presence of stargazin. Homomeric GluA1, GluA3, and GluA4 channels showed pronounced autoinactivation indicated by the bell-shaped steady-state dose response curves for glutamate. In contrast, homomeric GluA2i channels did not show significant autoinactivation. The resistance of GluA2 to autoinactivation showed striking dependence on the splice form as GluA2-flop receptors displayed clear autoinactivation. Interestingly, the resistance of GluA2-flip containing receptors to autoinactivation was transferred onto heteromeric receptors in a dominant fashion. To examine the relationship of autoinactivation to physical separation of stargazin from the AMPA receptor, we analyzed a GluA4-stargazin fusion protein. Notably, the covalently linked complex and separately expressed proteins expressed a similar level of autoinactivation. We conclude that autoinactivation is a subunit and splice form dependent property of AMPA receptor-stargazin complexes, which involves structural rearrangements within the complex rather than any physical dissociation. en
dc.format.extent 6
dc.language.iso eng
dc.relation.ispartof PLoS One
dc.rights en
dc.subject 1182 Biochemistry, cell and molecular biology en
dc.subject GluA en
dc.subject AMPA RECEPTOR en
dc.title Autoinactivation of the Stargazin–AMPA Receptor Complex: Subunit-Dependency and Independence from Physical Dissociation en
dc.type Article
dc.description.version Peer reviewed
dc.identifier.doi https://doi.org/10.1371/journal.pone.0049282
dc.type.uri info:eu-repo/semantics/other
dc.type.uri info:eu-repo/semantics/publishedVersion
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