S-nitrosylation of stargazin regulates surface expression of AMPA-glutamate neurotransmitter receptors.
Synaptic plasticity is mediated by changes in the surface expression of AMPA receptors (AMPARs). Stargazin and related transmembrane AMPAR regulatory proteins have emerged as the principal regulators of AMPAR surface expression. Here, we show in heterologous cells and primary neurons that stargazin is physiologically S-nitrosylated, resulting in increased surface expression. S-nitrosylation of stargazin increases binding to the AMPAR subunit GluR1, causing increased surface expression of the AMPAR. NMDAR stimulation, well known to activate neuronal nitric oxide synthase, increases both nitrosylation of stargazin and its binding to AMPAR. Thus, S-nitrosylation of stargazin is a physiologic regulator of AMPAR surface expression.
Selvakumar
Balakrishnan
B
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Huganir
Richard L
RL
Snyder
Solomon H
SH
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D015538:Nitrosation; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*
D015220:Calcium Channels; D052248:Nitric Oxide Synthase Type I; D018091:Receptors, AMPA; C491912:CACNG2 protein, human