Phosphorylation of Tyrosine 1070 at the GluN2B Subunit Is Regulated by Synaptic Activity and Critical for Surface Expression of N-Methyl-D-aspartate (NMDA) Receptors
Phosphorylation of Tyrosine 1070 at the GluN2B Subunit Is Regulated by Synaptic Activity and Critical for Surface Expression of N-Methyl-D-aspartate (NMDA) Receptors
复制标题
GluN2B 亚基上酪氨酸 1070 的磷酸化受突触活性调节，对 N-甲基-D-天冬氨酸 (NMDA) 受体的表面表达至关重要
DOI：
10.1074/jbc.m115.663450
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发表时间：
2015-09-01
影响因子：
4.8
通讯作者：
Yang, Wei
中科院分区：
文献类型：
--
作者：
Lu, Wen;Fang, Weiqing;Yang, Wei
突触N-甲基-D-天冬氨酸受体（NMDAR）的数量和亚基组成在突触可塑性、学习和记忆中起关键作用，并与神经系统疾病有关。酪氨酸磷酸化提供了一个强大的手段来调节NMDAR的功能，但底层机制仍然难以捉摸。在这项研究中，我们确定了一个酪氨酸位点上的GluN 2B亚基，酪氨酸-1070，这是磷酸化的原癌基因酪氨酸蛋白（Fyn）激酶和关键的表面表达的GluN 2B-含有NMDAR。GluN 2B在Tyr-1070处的磷酸化是Fyn激酶与GluN 2B结合所必需的，这上调了GluN 2B在Tyr-1472处的磷酸化。此外，我们的研究结果表明，GluN 2B在Tyr-1070磷酸化的变化伴随着Tyr-1472磷酸化和Fyn与GluN 2B相关的化学和背景恐惧学习的突触可塑性。总之，我们的研究结果提供了一个新的机制，调节NMDAR的表面表达与突触可塑性的影响。
The number and subunit composition of synaptic N-methyl-D-aspartate receptors (NMDARs) play critical roles in synaptic plasticity, learning, and memory and are implicated in neurological disorders. Tyrosine phosphorylation provides a powerful means of regulating NMDAR function, but the underling mechanism remains elusive. In this study we identified a tyrosine site on the GluN2B subunit, Tyr-1070, which was phosphorylated by a proto-oncogene tyrosine-protein (Fyn) kinase and critical for the surface expression of GluN2B-containing NMDARs. The phosphorylation of GluN2B at Tyr-1070 was required for binding of Fyn kinase to GluN2B, which up-regulated the phosphorylation of GluN2B at Tyr-1472. Moreover, our results revealed that the phosphorylation change of GluN2B at Tyr-1070 accompanied the Tyr-1472 phosphorylation and Fyn associated with GluN2B in synaptic plasticity induced by both chemical and contextual fear learning. Taken together, our findings provide a new mechanism for regulating the surface expression of NMDARs with implications for synaptic plasticity.