Selvakumar Balakrishnan, Huganir Richard L, Snyder Solomon H
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16440-5. doi: 10.1073/pnas.0908949106. Epub 2009 Sep 10.
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.
突触可塑性由α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPARs）的表面表达变化介导。γ-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体γ-亚基（stargazin）及相关跨膜AMPAR调节蛋白已成为AMPAR表面表达的主要调节因子。在此，我们在异源细胞和原代神经元中发现，stargazin在生理状态下会发生S-亚硝基化，导致其表面表达增加。stargazin的S-亚硝基化增加了与AMPAR亚基GluR1的结合，从而导致AMPAR的表面表达增加。众所周知，N-甲基-D-天冬氨酸受体（NMDAR）刺激可激活神经元型一氧化氮合酶，增加stargazin的亚硝基化及其与AMPAR的结合。因此，stargazin的S-亚硝基化是AMPAR表面表达的生理调节因子。
