S-Nitrosylation of AMPA receptor GluA1 regulates phosphorylation, single-channel conductance, and endocytosis

Solomon H. Snyder Department of Neuroscience and Departments of Psychiatry and Behavioral Sciences, Pharmacology and Molecular Sciences, and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 12/2012; 110(3). DOI: 10.1073/pnas.1221295110
Source: PubMed


NMDA receptor activation can elicit synaptic plasticity by augmenting conductance of the AMPA receptor GluA1 subsequent to phosphorylation at S831 by Ca(2+)-dependent kinases. NMDA receptor activation also regulates synaptic plasticity by causing endocytosis of AMPA receptor GluA1. We demonstrate a unique signaling cascade for these processes mediated by NMDA receptor-dependent NO formation and GluA1 S-nitrosylation. Thus, S-nitrosylation of GluA1 at C875 enhances S831 phosphorylation, facilitates the associated AMPA receptor conductance increase, and results in endocytosis by increasing receptor binding to the AP2 protein of the endocytotic machinery.

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