Stabilization of Ca super(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. Certaintypes of neural activity can recruit Ca super(2+)-permeable (CP) AMPARs, such as GluR1 homomers, to synapses likely via lateral diffusion from extrasynaptic sites. Here weshow t...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-01, Vol.106 (47), p.20033-20038
Main Authors: He, Kaiwen, Song, Lihua, Cummings, Laurel W, Goldman, Jonathan, Huganir, Richard L, Lee, Hey-Kyoung
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:AMPA receptor (AMPAR) channel properties and function are regulated by its subunit composition and phosphorylation. Certaintypes of neural activity can recruit Ca super(2+)-permeable (CP) AMPARs, such as GluR1 homomers, to synapses likely via lateral diffusion from extrasynaptic sites. Here weshow that GluR1-S845 phosphorylation can alter the subunit composition of perisynaptic AMPARs by providing stability to GluR1homomers. Using mice specifically lacking phosphorylation of the GluR1-S845 site (GluR1-S845A mutants), we demonstrate thatthis site is necessary for maintaining CP-AMPARs. Specifically, in the GluR1-S845A mutants, CP-AMPARs were absent from perisynapticlocations mainly due to lysosomal degradation. This regulation was mimicked by acute desphosphorylation of the GluR1-S845site in wild-type mice by NMDA application. Furthermore, long-term depression (LTD) was associated with a reduction in perisynapticCP-AMPAR levels. Our findings suggest that GluR1-S845 is necessary for maintaining CP-AMPARs on the surface, especially atperisynaptic sites, and suggest that the regulation of these receptors is involved in synaptic plasticity.
ISSN:0027-8424
DOI:10.1073/pnas.0910338106