Stabilization of Ca^sup 2+^-permeable AMPA receptors at perisynaptic sites by GluR1-S845 phosphorylation

AMPA receptor (AMPAR) channel properties and function are regulated by its subunit composition and phosphorylation. Certain types of neural activity can recruit Ca...-permeable (CP) AMPARs, such as GluR1 homomers, to synapses likely via lateral diffusion from extrasynaptic sites. Here we show that G...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-11, Vol.106 (47), p.20033
Main Authors: He, Kaiwen, Song, Lihua, Cummings, Laurel W, Goldman, Jonathan, Huganir, Richard L, Lee, Hey-Kyoung
Format: Article
Language:English
Subjects:
Calcium
Mental depression
Mutation
Neurons
Rodents
Online Access:Get full text
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Summary:AMPA receptor (AMPAR) channel properties and function are regulated by its subunit composition and phosphorylation. Certain types of neural activity can recruit Ca...-permeable (CP) AMPARs, such as GluR1 homomers, to synapses likely via lateral diffusion from extrasynaptic sites. Here we show that GluR1-S845 phosphorylation can alter the subunit composition of perisynaptic AMPARs by providing stability to GluR1 homomers. Using mice specifically lacking phosphorylation of the GluR1-S845 site (GluR1-S845A mutants), we demonstrate that this site is necessary for maintaining CP-AMPARs. Specifically, in the GluR1-S845A mutants, CP-AMPARs were absent from perisynaptic locations mainly due to lysosomal degradation. This regulation was mimicked by acute desphosphorylation of the GluR1-S845 site in wild-type mice by NMDA application. Furthermore, long-term depression (LTD) was associated with a reduction in perisynaptic CP-AMPAR levels. Our findings suggest that GluR1-S845 is necessary for maintaining CP-AMPARs on the surface, especially at perisynaptic sites, and suggest that the regulation of these receptors is involved in synaptic plasticity. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:0027-8424
1091-6490