Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases
Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases
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DOI：
10.1523/jneurosci.16-07-02157.1996
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发表时间：
1996-04
期刊：
影响因子：
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通讯作者：
Martin Niethammer;Eunjoon Kim;Morgan Sheng
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文献类型：
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作者：
Martin Niethammer;Eunjoon Kim;Morgan Sheng
突触上亲电离子受体的选择性聚集和锚定是神经元信号传递的关键。人们对中枢神经系统中调节受体聚集的分子知之甚少。用酵母双杂交系统筛选大鼠脑内cDNA库，通过体外结合实验，我们鉴定了NMDA受体亚单位2A和2B(NR2A和NR2B)与PSD-95/SAP90家族中的三个不同成员之间的相互作用。这种相互作用是通过NMDA受体亚基的C末端与PSD-95/SAP90的前两个PDZ(也称为GLGF或DHR)结构域结合而实现的，PSD-95/SAP90是一种与膜细胞骨架相关的丰富的突触蛋白。PSD-95也是已知的结合和聚集振荡型电压门控K+通道。NR2亚基的C末端和K+通道之间的相似性表明PDZ结构域有一个共同的C末端结合基序。这些数据表明，PDZ结构域可以作为蛋白质-蛋白质相互作用的模块。PSD-95家族的成员可能起到将NMDA受体锚定到膜下细胞骨架上，并帮助在突触后部位组装信号转导复合体的作用。
Selective concentration and anchoring of ionotropic receptors at the synapse is essential for neuronal signaling. Little is known about the molecules that mediate receptor clustering in the CNS. With use of the yeast two-hybrid system to screen a rat brain cDNA library and by in vitro binding assays, we have identified an interaction between NMDA receptor subunits 2A and 2B (NR2A and NR2B) and three distinct members of the PSD-95/SAP90 family of membrane-associated putative guanylate kinases. The interaction is mediated by binding of the C terminus of the NMDA receptor subunits to the first two PDZ (also known as GLGF or DHR) domains of PSD-95/SAP90, an abundant synaptic protein associated with the membrane cytoskeleton. PSD-95 is also known to bind and cluster Shaker-type voltage-gated K+ channels. Similarities between the C-termini of NR2 subunits and K+ channels suggest a common C-terminal binding motif for PDZ domains. These data suggest that PDZ domains can function as modules for protein-protein interactions. Members of the PSD-95 family might serve to anchor NMDA receptors to the submembrane cytoskeleton and aid in the assembly of signal transduction complexes at postsynaptic sites.