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Molecular mechanisums of regulation of NMDA receptor by post-synaptic density proteins

突触后密度蛋白调控NMDA受体的分子机制

基本信息

批准号：
12680755
负责人：
YAMADA Yasue
金额：
$ 2.3万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680755/
关键词：
NMPA recptor PSD-95 MALS-2 PDZ proteins Xenopus oocyte PKC Src insulin PDZ protein グルタミン酸受容体 Xenopus oocyte 二電極膜電位固定法チロシンリン酸化酵素プロテインキナーゼC 亜鉛

项目摘要

The NMDA receptors is essential for the induction of long term potentiation (LTP) which is thought to plays a key role in synaptic plasticity underlying memory and learning. The NMDA receptor usually makes the complex with post-synaptic density proteins including PSD-95. MALS-2 and α-actinin. It is unknown how those proteins regulate the channel activity of the NMDA receptor. In this study, we examined the effects of PSD-95 on four )ε1/ζ1, ε2/ζ1, ε3/ζ1 and ε4/ζ1) subtypes of the NMDA receptor by injection of PSD-95 CRNA into Xenopus oocytes expressing the receptors. We also examined the effects of another PDZ protein, MALS-2, on the channel activity of the NMDA receptor. PSD-95 inhibited the protein kinase C (PKC) - mediated potentiation ofε1/ζ1 and ε2/ζ1 and the Src-mediated potentiation of ε1/ζ1. It has been reported that insulin potentiates the currents of the ε1/ζ1, ε2/ζ1, ε3/ζ1 and ε4/ζ1. Co-expressing of PSD-95 eliminated the insulin-induced potentiation of all four subtypes. MALS-2 dose not eliminate the potentiation of the channels by PKC, Src and insulin. We demonstrated that post-synaptic density proteins, like PSD-95 and MALS-2, functionally modulate the channel activity of NMDA receptor.

NMDA受体是诱导长时程增强（LTP）的关键，LTP被认为在记忆和学习的突触可塑性中起关键作用。NMDA受体通常与包括PSD-95在内的突触后密度蛋白形成复合物。MALS-2和α-辅肌动蛋白。目前还不清楚这些蛋白质如何调节NMDA受体的通道活性。在这项研究中，我们通过将PSD-95 CRNA注射到表达NMDA受体的非洲爪蟾卵母细胞中来检测PSD-95对四种（ε1/ε 1，ε2/ε 1，ε3/ε 1和ε4/ε 4）亚型NMDA受体的影响。我们还研究了另一种PDZ蛋白MALS-2对NMDA受体通道活性的影响。PSD-95抑制蛋白激酶C（PKC）介导的ε1/ε2/ε 1增强和Src介导的ε1/ε 1增强。据报道，胰岛素可增强ε1/ε 1、ε2/ε 2、ε3/ε 3和ε4/ε 4的电流。PSD-95的共表达消除了所有四种亚型的胰岛素诱导的增强作用。MALS-2不能消除PKC、Src和胰岛素对通道的增强作用。我们证明，突触后密度蛋白，如PSD-95和MALS-2，功能调节NMDA受体的通道活动。