Stabilization of Ca2+-permeable AMPA receptors at perisynaptic sites by GluR1-S845 phosphorylation |
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| Authors: | Kaiwen He Lihua Song Laurel W. Cummings Jonathan Goldman Richard L. Huganir Hey-Kyoung Lee |
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| Affiliation: | aDepartment of Biology, College of Chemical and Life Sciences and ;bNeuroscience and Cognitive Science (NACS) Program, University of Maryland, College Park, MD 20742; and ;cSolomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, MD 21210 |
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| 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. |
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| Keywords: | excitatory synaptic transmission GluR1 homomer |
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