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

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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

Title: Autoinactivation of the Stargazin–AMPA Receptor Complex: Subunit-Dependency and Independence from Physical Dissociation
Author: Semenov, Artur; Möykkynen, Tommi Petteri; Korpi, Esa Risto; Coleman, Sarah Kate; Keinänen, Kari
Contributor: University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Biosciences
University of Helsinki, Biosciences
Date: 2012
Language: eng
Number of pages: 6
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/42084
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.
Subject: 1182 Biochemistry, cell and molecular biology
GluA
AMPA RECEPTOR
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