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PNAS 110 (3): 1077-1082

Copyright © 2013 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / NEUROSCIENCE

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

Balakrishnan Selvakumara, Meagan A. Jenkinsb, Natasha K. Hussaina, Richard L. Huganira,c, Stephen F. Traynelisb, and Solomon H. Snydera,d,e,1

aSolomon H. Snyder Department of Neuroscience and Departments of dPsychiatry and Behavioral Sciences, ePharmacology and Molecular Sciences, and cHoward Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; and bDepartment of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322

Contributed by Solomon H. Snyder, December 6, 2012 (sent for review November 13, 2012)

Abstract: NMDA receptor activation can elicit synaptic plasticity by augmenting conductance of the AMPA receptor GluA1 subsequent to phosphorylation at S831 by Ca2+-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.

Author contributions: B.S., R.L.H., and S.H.S. designed research; B.S., M.A.J., and N.K.H. performed research; B.S., M.A.J., N.K.H., R.L.H., S.F.T., and S.H.S. analyzed data; and B.S., M.A.J., R.L.H., S.F.T., and S.H.S. wrote the paper.

The authors declare no conflict of interest.

1To whom correspondence should be addressed. E-mail: ssnyder{at}jhmi.edu.

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Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882