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Author Notes:

To whom correspondence should be addressed. E-mail: ssnyder@jhmi.edu

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.

We thank Roxanne Barrow for excellent technical help; Lynda Hester for preparing dissociated neuronal cultures of the neocortex; Masoumeh Saleh for maintenance and genotyping of nNOS knockout mice; Gareth Thomas, Jean-Claude Béïque, and Myoung-Goo Kang for discussions pertaining to AMPAR biology; and past and present members of the Snyder laboratory for helpful discussions.

The authors declare no conflict of interest.

Subjects:

Research Funding:

This work was supported by US Public Health Service Grants MH18501 (to S.H.S.), NS36715 (to R.L.H.), and NS068464 (to S.F.T.).

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • MULTIDISCIPLINARY SCIENCES
  • LONG-TERM POTENTIATION
  • PROTEIN-KINASE-II
  • NITRIC-OXIDE
  • GLUTAMATE RECEPTORS
  • SYNAPTIC PLASTICITY
  • MEDIATED TRANSMISSION
  • SURFACE EXPRESSION
  • ENDOTHELIAL-CELLS
  • GLUR1 SUBUNIT
  • C ACTIVITY

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

Tools:

Journal Title:

Proceedings of the National Academy of Sciences

Volume:

Volume 110, Number 3

Publisher:

, Pages 1077-1082

Type of Work:

Article | Final Publisher PDF

Abstract:

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.

Copyright information:

© Selvakumar et al.

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