Kim E, Sheng M
Howard Hughes Medical Institute, Department of Neurobiology, Massachusetts General Hospital, Boston 02114, USA.
Neuropharmacology. 1996;35(7):993-1000. doi: 10.1016/0028-3908(96)00093-7.
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.
钾离子通道在神经元表面特定微结构域中聚集和定位的分子机制目前仍不清楚。电压门控钾离子通道α亚基的Shaker亚类通过其胞质C末端与一类膜相关的假定鸟苷酸激酶相互作用，包括PSD - 95和SAP97。我们在此表明，sap97或PSD - 95与各种Shaker型亚基的异源共表达导致这些蛋白质与钾离子通道共聚集。Shaker亚基Kv1.4的C末端序列（-ETDV）突变消除了其与SAP97和PSD - 95的结合，并阻止其与它们聚集。虽然PSD - 95在细胞表面诱导钾离子通道形成斑块状簇；然而，SAP97共表达导致形成大的圆形细胞内聚集体，其中SAP97和钾离子通道蛋白都共定位。PSD - 95对表面聚集的效率因不同的Shaker亚基而异：在超过60%的共转染细胞中发生显著的Kv1.4聚集，而Kv1.β和Kv1.2仅在大约10%的细胞中与PSD - 95形成令人信服的簇。 （注：原文中Kv1.β表述有误，推测应为Kv1.1，译文按Kv1.1翻译）
