Direct interaction of CASK/LIN-2 and syndecan heparan sulfate proteoglycan and their overlapping distribution in neuronal synapses.
Direct interaction of CASK/LIN-2 and syndecan heparan sulfate proteoglycan and their overlapping distribution in neuronal synapses.
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DOI：
10.1083/jcb.142.1.139
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发表时间：
1998-07-13
期刊：
影响因子：
--
通讯作者：
Sheng M
中科院分区：
文献类型：
--
作者：
Hsueh YP;Yang FC;Kharazia V;Naisbitt S;Cohen AR;Weinberg RJ;Sheng M
CASK是秀丽线虫外阴分化所需基因(Lin-2)的大鼠同源基因，在哺乳动物脑中表达，但其在神经元中的功能尚不清楚。CASK在神经元中呈点状体树突状分布。通过免疫金EM，CASK蛋白集中在突触中，但也存在于非突触膜和细胞内隔膜中。这一免疫定位与生化研究结果一致，表明CASK存在于大鼠脑内的可溶膜和突触体膜部分，并在突触后密度部分富含。通过酵母双杂交筛选，发现CASK的PDZ结构域与细胞表面硫酸乙酰肝素蛋白多糖(HSPG)Syndecan-2的COOH末端存在特异性的相互作用。异种细胞的免疫共沉淀证实了这种相互作用。在大脑中，Syndecan-2专门定位于突触连接处，在那里它与木桶重叠分布，这与突触中这些蛋白质之间的相互作用一致。细胞表面的HSPG能与细胞外基质蛋白结合，是多种肝素结合多肽生长/分化因子所必需的。CASK和Syndecan的突触定位表明，这些蛋白在神经元突触的黏附和信号传递中具有潜在的作用。
CASK, the rat homolog of a gene (LIN-2) required for vulval differentiation in Caenorhabditis elegans, is expressed in mammalian brain, but its function in neurons is unknown. CASK is distributed in a punctate somatodendritic pattern in neurons. By immunogold EM, CASK protein is concentrated in synapses, but is also present at nonsynaptic membranes and in intracellular compartments. This immunolocalization is consistent with biochemical studies showing the presence of CASK in soluble and synaptosomal membrane fractions and its enrichment in postsynaptic density fractions of rat brain. By yeast two-hybrid screening, a specific interaction was identified between the PDZ domain of CASK and the COOH terminal tail of syndecan-2, a cell surface heparan sulfate proteoglycan (HSPG). The interaction was confirmed by coimmunoprecipitation from heterologous cells. In brain, syndecan-2 localizes specifically at synaptic junctions where it shows overlapping distribution with CASK, consistent with an interaction between these proteins in synapses. Cell surface HSPGs can bind to extracellular matrix proteins, and are required for the action of various heparin-binding polypeptide growth/differentiation factors. The synaptic localization of CASK and syndecan suggests a potential role for these proteins in adhesion and signaling at neuronal synapses.