Differential K+ channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases
Differential K+ channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases
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DOI：
10.1016/0028-3908(96)00093-7
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发表时间：
1996-07-01
影响因子：
4.7
通讯作者：
Sheng, M
中科院分区：
文献类型：
--
作者：
Kim, E;Sheng, M
K+通道在神经元表面特定微区的聚集和定位的分子机制在很大程度上是未知的。电压门控K+通道α亚基的Shaker亚类通过其细胞质C-末端与膜相关推定鸟苷酸激酶家族（包括PSD-95和SAP 97）相互作用。我们在这里表明，SAP 97或PSD-95与各种Shaker型亚基的异源共表达导致这些蛋白质与K+通道的共聚集。Shaker亚基Kv1.4的C-末端序列（-ETDV）的突变消除了其与SAP 97和PSD-95的结合，并防止其与SAP 97和PSD-95的聚类。而PSD-95诱导细胞表面的K+通道的斑块样簇;然而，SAP 97共表达导致形成大的圆形细胞内聚集体，其中SAP 97和K+通道蛋白共定位。PSD-95的表面聚集效率随Shaker亚基的不同而变化：在>60%的共转染细胞中出现了显著的Kv1.4聚集，而Kv1.1和Kv1.2仅在约10%的细胞中与PSD-95形成令人信服的簇。版权所有（C）1996 Elsevier Science Ltd
The molecular mechanisms underlying the clustering and localization of K+ channels in specific microdomains on the neuronal surface are largely unknown. The Shaker subclass of voltage-gated K+ channel alpha-subunits interact through their cytoplasmic C-terminus with a family of membrane-associated putative guanylate kinases, including PSD-95 and SAP97. We show here that heterologous coexpression of either SAP97 or PSD-95 with various Shaker-type subunits results in the coclustering of these proteins with the K+ channels. Mutation of the C-terminal sequence (-ETDV) of the Shaker subunit Kv1.4 abolishes its binding to, and prevents its clustering with, SAP97 and PSD-95. Whereas PSD-95 induces plaque-like clusters of K+ channels at the cell surface; however, SAP97 coexpression results in the formation of large round intracellular aggregates into which both SAP97 and the K+ channel proteins are colocalized. The efficiency of surface clustering by PSD-95 varies with different Shaker subunits: striking Kv1.4 clustering occurs in >60% of cotransfected cells, whereas Kv1.1 and Kv1.2 form convincing clusters with PSD-95 only in approximately 10% of cells. Copyright (C) 1996 Elsevier Science Ltd