GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules.
GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules.
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DOI：
10.1083/jcb.136.3.669
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发表时间：
1997-02-10
期刊：
影响因子：
--
通讯作者：
Sheng M
中科院分区：
文献类型：
--
作者：
Kim E;Naisbitt S;Hsueh YP;Rao A;Rothschild A;Craig AM;Sheng M
突触连接处离子通道和信号分子组织的分子机制在很大程度上是未知的。最近，突触MAGUK(膜相关鸟苷酸激酶)PSD-95/SAP90家族的成员被证明通过其NH2末端的PDZ结构域与某些离子通道(NMDA受体和K+通道)相互作用，从而促进这些蛋白的聚集。尽管NH2-末端PDZ结构域的功能已被较好地描述，但在PSD-95的COOH-末端半部分中，Src同源3(SH3)结构域和鸟氨酸激酶样(GK)结构域的功能仍不清楚。我们现在报告分离到一种新的突触蛋白，称为鸟苷酸激酶相关蛋白，它直接与哺乳动物PSD-95家族四个已知成员的GK结构域结合。GKAP显示出独特的结构域结构，似乎是突触后密度的主要组成部分。GKAP在体内与PSD-95共定位和免疫共沉淀，在异种细胞中与PSD-95和K+通道/NMDA受体共聚集。鉴于它们明显缺乏鸟苷酸激酶的活性，GK结构域可以作为蛋白质-蛋白质相互作用的位点这一事实对各种含有GK的蛋白质(如P55、ZO-1和LIN-2/CAASK)的功能具有一定的意义。
The molecular mechanisms underlying the organization of ion channels and signaling molecules at the synaptic junction are largely unknown. Recently, members of the PSD-95/SAP90 family of synaptic MAGUK (membrane-associated guanylate kinase) proteins have been shown to interact, via their NH2-terminal PDZ domains, with certain ion channels (NMDA receptors and K+ channels), thereby promoting the clustering of these proteins. Although the function of the NH2-terminal PDZ domains is relatively well characterized, the function of the Src homology 3 (SH3) domain and the guanylate kinase-like (GK) domain in the COOH-terminal half of PSD-95 has remained obscure. We now report the isolation of a novel synaptic protein, termed GKAP for guanylate kinase-associated protein, that binds directly to the GK domain of the four known members of the mammalian PSD-95 family. GKAP shows a unique domain structure and appears to be a major constituent of the postsynaptic density. GKAP colocalizes and coimmunoprecipitates with PSD-95 in vivo, and coclusters with PSD-95 and K+ channels/ NMDA receptors in heterologous cells. Given their apparent lack of guanylate kinase enzymatic activity, the fact that the GK domain can act as a site for protein– protein interaction has implications for the function of diverse GK-containing proteins (such as p55, ZO-1, and LIN-2/CASK).