Solomon H Snyder Department of Neuroscience and Departments of Psychiatry and Behavioral Sciences, Pharmacology and Molecular Sciences, and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):1077-82. doi: 10.1073/pnas.1221295110. Epub 2012 Dec 31.
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.
NMDA 受体的激活可通过 Ca(2+)-依赖性激酶使 AMPA 受体 GluA1 的 S831 磷酸化来增强其电导,从而引发突触可塑性。NMDA 受体的激活还通过引起 AMPA 受体 GluA1 的内吞作用来调节突触可塑性。我们证明了一种独特的信号级联反应,介导 NMDA 受体依赖性 NO 形成和 GluA1 S-亚硝化为这些过程。因此,GluA1 的 C875 处的 S-亚硝化增强 S831 磷酸化,促进相关的 AMPA 受体电导增加,并通过增加受体与内吞机制的 AP2 蛋白的结合而导致内吞。