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

• Authors: Balakrishnan Selvakumar, Johns Hopkins University; Meagan A. Jenkins, Emory University; Natasha K. Hussain, Johns Hopkins University; Richard L. Huganir, Johns Hopkins University; Stephen Traynelis, Emory University; Solomon H. Snyder Snyder, Johns Hopkins University
• Journal Title: Proceedings of the National Academy of Sciences
• Volume: Volume 110, Number 3
• Publisher: National Academy of Sciences | 2013-01-15, Pages 1077-1082
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1073/pnas.1221295110
• Subjects: Biology, Neuroscience; Psychology, Behavioral; Health Sciences, Pharmacology
• 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

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.