CLUSTERING OF SHAKER-TYPE K+ CHANNELS BY INTERACTION WITH A FAMILY OF MEMBRANE-ASSOCIATED GUANYLATE KINASES
CLUSTERING OF SHAKER-TYPE K+ CHANNELS BY INTERACTION WITH A FAMILY OF MEMBRANE-ASSOCIATED GUANYLATE KINASES
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DOI：
10.1038/378085a0
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发表时间：
1995-11-02
期刊：
影响因子：
64.8
通讯作者：
SHENG, M
中科院分区：
文献类型：
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作者：
KIM, E;NIETHAMMER, M;SHENG, M
离子通道在特定亚细胞位点的锚定对于神经元信号传导至关重要，但通道定位和聚集的潜在机制在很大程度上是未知的（参考文献1综述）。电压门控K⁺通道集中在各种神经元区域，包括突触前末梢、郎飞结和树突，在这些部位它们调节局部膜的兴奋性。在此我们提供了功能和生化证据，表明Shaker亚家族K⁺通道的细胞表面聚集是由膜相关的假定鸟苷酸激酶PSD - 95家族介导的，这是由于K⁺通道亚基的羧基末端胞质尾直接结合到PSD - 95蛋白中的两个PDZ（也称为GLGF或DHR）结构域（2）。PDZ结构域作为蛋白质 - 蛋白质相互作用的独立模块的能力，以及它们在其他连接相关分子（如ZO - 1（参考文献3）和 syntrophin（4））中的存在，表明含PDZ结构域的多肽可能广泛参与膜特化部位的蛋白质组织。
ANCHORING Of ion channels at specific subcellular sites is critical for neuronal signalling, but the mechanisms underlying channel localization and clustering are largely unknown (reviewed in ref. 1). Voltage-gated K+ channels are concentrated in various neuronal domains, including presynaptic terminals, nodes of Ranvier and dendrites, where they regulate local membrane excitability. Here we present functional and biochemical evidence that cell-surface clustering of Shaker-subfamily K+ channels is mediated by the PSD-95 family of membrane-associated putative guanylate kinases, as a result of direct binding of the carboxy-terminal cytoplasmic tails of the K+ channel subunits to two PDZ (also known as GLGF or DHR) domains in the PSD-95 protein(2). The ability of PDZ domains to function as independent modules for protein-protein interaction, and their presence in other junction-associated molecules (such as ZO-1 (ref. 3) and syntrophin(4)), suggest that PDZ-domain-containing polypeptides may be widely involved in the organization of proteins at sites of membrane specialization.