PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A
PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A
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DOI：
10.1073/pnas.96.2.435
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发表时间：
1999-01-19
影响因子：
11.1
通讯作者：
Yamamoto, T
中科院分区：
文献类型：
--
作者：
Tezuka, T;Umemori, H;Yamamoto, T
Fyn是Src家族蛋白酪氨酸激酶（PTK）的一员，参与涉及N-甲基-D-天冬氨酸（NMDA）受体功能的学习和记忆。本研究通过分析Fyn与NMDA受体之间的物理和功能相互作用，探讨了Fyn在突触可塑性中的作用机制。NR 2A在293 T细胞中与Fyn共表达时酪氨酸磷酸化。因此，NR 2A将是Fyn在体内的底物。PSD-95可直接与NMDA受体结合，并与NMDA受体共簇，促进Fyn介导的NR 2A酪氨酸磷酸化。PSD-95的不同区域分别与NR 2A和Fyn结合，因此PSD-95可介导Fyn与NR 2A形成复合物。PSD-95还与其他Src家族PTK Src、Yes和林恩相关。这些结果表明PSD-95对于Fyn和其他Src家族PTK调节NMDA受体活性至关重要，作为将这些PTK锚定到NR 2A的分子支架。
Fyn, a member of the Src-family protein-tyrosine kinase (PTK), is implicated in learning and memory that involves iv-methyl-D-aspartate (NMDA) receptor function. In this study, we examined how Fyn participates in synaptic plasticity by analyzing the physical and functional interaction between Fyn and NMDA receptors, Results showed that tyrosine phosphorylation of NR2A, one of the NMDA receptor subunits, was reduced in fyn-mutant mice. NR2A was tyrosine phosphorylated in 293T cells when coexpressed with Fyn. Therefore, NR2A would be a substrate for Fyn in vivo. Results also showed that PSD-95, which directly binds to and coclusters with NMDA receptors, promotes Fyn-mediated tyrosine phosphorylation of NR2A, Different regions of PSD-95 associated with NR2A and Fyn, respectively, and so PSD-95 could mediate complex formation of Fyn with NR2A. PSD-95 also associated with other Src-family PTKs, Src, Yes, and Lyn. These results suggest that PSD-95 is critical for regulation of NMDA receptor activity by Fyn and other Src-family PTKs, serving as a molecular scaffold for anchoring these PTKs to NR2A.