Differential interaction of NMDA receptor subtypes with the post-synaptic density-95 family of membrane associated guanylate kinase proteins
Differential interaction of NMDA receptor subtypes with the post-synaptic density-95 family of membrane associated guanylate kinase proteins
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DOI：
10.1111/j.1471-4159.2007.05067.x
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发表时间：
2008-02-01
影响因子：
4.7
通讯作者：
Stephenson, F. Anne
中科院分区：
文献类型：
--
作者：
Cousins, Sarah L.;Papadakis, Michalis;Stephenson, F. Anne
NMDA受体是离子型谷氨酸受体的一个亚类。它们通过支架蛋白的突触后密度（PSD）-95膜相关鸟苷酸激酶（MAGUK）家族被运输和/或聚集在突触处，所述支架蛋白通过其C-末端谷氨酸丝氨酸（天冬氨酸/谷氨酸）缬氨酸基序与NMDA受体NR 2亚基缔合。我们已经进行了系统的研究调查在异源表达系统中，协会的四个主要NMDA受体亚型与PSD-95家族的MAGUK蛋白，chapsyn-110，PSD-95，突触相关蛋白（SAP）97和SAP 102。我们报告说，尽管每种PSD-95 MAGUK均显示与NR 1/NR 2A、NR 1/NR 2B、NR 1/NR 2C和NR 1/NR 2D受体亚型发生免疫共沉淀，但它们在增强总NR 2亚基表达方面引起了不同的作用，从而导致细胞表面表达增加。NMDA受体亚型。PSD-95和chapsyn-110增强NR 2A和NR 2B的总表达，导致NR 1/NR 2A和NR 1/NR 2B受体细胞表面表达增加，而SAP 97和SAP 102对这些亚型的总表达或细胞表面表达没有影响。PSD-95、Chapsyn-110、SAP 97和SAP 102对NR 2C和NR 2D亚基的总表达以及细胞表面NR 1/NR 2C和NR 1/NR 2D的表达均无影响。PSD-95 α、PSD-95 β和PSD-95 α（C3 S、C5 S）的比较表明，PSD-95增强的NR 1/NR 2A受体的细胞表面表达依赖于PSD-95 N-末端C3、C5半胱氨酸。这些观察结果支持NMDA受体亚型与不同PSD-95 MAGUK支架蛋白的差异相互作用。这对发育过程中神经元和成熟大脑中NMDA受体亚型的稳定、周转和区室化具有影响。
NMDA receptors are a subclass of ionotropic glutamate receptors. They are trafficked and/or clustered at synapses by the post-synaptic density (PSD)-95 membrane associated guanylate kinase (MAGUK) family of scaffolding proteins that associate with NMDA receptor NR2 subunits via their C-terminal glutamate serine (aspartate/glutamate) valine motifs. We have carried out a systematic study investigating in a heterologous expression system, the association of the four major NMDA receptor subtypes with the PSD-95 family of MAGUK proteins, chapsyn-110, PSD-95, synapse associated protein (SAP) 97 and SAP102. We report that although each PSD-95 MAGUK was shown to co-immunoprecipitate with NR1/NR2A, NR1/NR2B, NR1/NR2C and NR1/NR2D receptor subtypes, they elicited differential effects with regard to the enhancement of total NR2 subunit expression which then results in an increased cell surface expression of NMDA receptor subtypes. PSD-95 and chapsyn-110 enhanced NR2A and NR2B total expression which resulted in increased NR1/NR2A and NR1/NR2B receptor cell surface expression whereas SAP97 and SAP102 had no effect on total or cell surface expression of these subtypes. PSD-95, chapsyn-110, SAP97 and SAP102 had no effect on either total NR2C and NR2D subunit expression or cell surface NR1/NR2C and NR1/NR2D expression. A comparison of PSD-95 alpha, PSD-95(3 and PSD-95 alpha(C3S,C5S) showed that PSD-95-enhanced cell surface expression of NR1/NR2A receptors was dependent upon the PSD-95 N-terminal C3,C5 cysteines. These observations support differential interaction of NMDA receptor subtypes with different PSD-95 MAGUK scaffolding proteins. This has implications for the stabilisation, turnover and compartmentalisation of NMDA receptor subtypes in neurones during development and in the mature brain.