Diering Graham H, Heo Seok, Hussain Natasha K, Liu Bian, Huganir Richard L
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205; Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD 21205
Proc Natl Acad Sci U S A. 2016 Aug 16;113(33):E4920-7. doi: 10.1073/pnas.1610631113. Epub 2016 Aug 1.
Regulation of AMPA receptor (AMPAR) function is a fundamental mechanism controlling synaptic strength during long-term potentiation/depression and homeostatic scaling. AMPAR function and membrane trafficking is controlled by protein-protein interactions, as well as by posttranslational modifications. Phosphorylation of the GluA1 AMPAR subunit at S845 and S831 play especially important roles during synaptic plasticity. Recent controversy has emerged regarding the extent to which GluA1 phosphorylation may contribute to synaptic plasticity. Here we used a variety of methods to measure the population of phosphorylated GluA1-containing AMPARs in cultured primary neurons and mouse forebrain. Phosphorylated GluA1 represents large fractions from 12% to 50% of the total population under basal and stimulated conditions in vitro and in vivo. Furthermore, a large fraction of synapses are positive for phospho-GluA1-containing AMPARs. Our results support the large body of research indicating a prominent role of GluA1 phosphorylation in synaptic plasticity.
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）功能的调节是在长时程增强/抑制和稳态缩放过程中控制突触强度的基本机制。AMPAR功能和膜转运受蛋白质-蛋白质相互作用以及翻译后修饰的控制。GluA1 AMPAR亚基在S845和S831位点的磷酸化在突触可塑性过程中发挥着尤为重要的作用。最近，关于GluA1磷酸化对突触可塑性的贡献程度出现了争议。在这里，我们使用了多种方法来测量培养的原代神经元和小鼠前脑中含磷酸化GluA1的AMPAR的数量。在体外和体内的基础和刺激条件下，磷酸化的GluA1占总数的很大比例，从12%到50%不等。此外，很大一部分突触对含磷酸化GluA1的AMPAR呈阳性。我们的结果支持了大量的研究，表明GluA1磷酸化在突触可塑性中起着重要作用。
