Stabilization of Ca2+-permeable AMPA receptors at perisynaptic sites by GluR1-S845 phosphorylation

Kaiwen He, Lihua Song, Laurel W. Cummings, Jonathan Goldman, Richard L. Huganir, Hey Kyoung Lee

Research output: Contribution to journalArticlepeer-review

Abstract

AMPA receptor (AMPAR) channel properties and function are regulated by its subunit composition and phosphorylation. Certain types of neural activity can recruit Ca2+-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.

Original languageEnglish (US)
Pages (from-to)20033-20038
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number47
DOIs
StatePublished - Nov 24 2009

Keywords

  • Excitatory synaptic transmission
  • GluR1 homomer

ASJC Scopus subject areas

  • General

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