Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin
Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin
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DOI：
10.1016/s0896-6273(00)80809-0
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发表时间：
1999-07-01
期刊：
影响因子：
16.2
通讯作者：
Sheng, M
中科院分区：
文献类型：
--
作者：
Naisbitt, S;Kim, E;Sheng, M
N - 甲基 - D - 天冬氨酸（NMDA）受体通过突触后密度蛋白95（PSD - 95）蛋白复合物与细胞内细胞骨架及信号分子相连接。我们报道了一个新的突触后密度（PSD）蛋白家族，称为Shank，它通过其PDZ结构域与PSD - 95相关蛋白GKAP的C末端结合。Shank / GKAP / PSD - 95三元复合物在异源细胞中组装，并且可以从大鼠脑中进行免疫共沉淀。Shank在神经元中的突触定位受到一种缺乏Shank结合C末端的GKAP剪接变体的抑制。除了其PDZ结构域，Shank还包含一个能与辅肌动蛋白结合的富含脯氨酸的区域以及一个介导多聚化的无规卷曲α - 螺旋（SAM）结构域。Shank可能在PSD中作为一种支架蛋白发挥作用，潜在地使NMDA受体/ PSD - 95复合物交联，并将它们与肌动蛋白细胞骨架的调节因子偶联。
NMDA receptors are linked to intracellular cytoskeletal and signaling molecules via the PSD-95 protein complex. We report a novel family of postsynaptic density (PSD) proteins, termed Shank, that binds via its PDZ domain to the C terminus of PSD-95-associated protein GKAP. A ternary complex of Shank/GKAP/PSD-95 assembles in heterologous cells and can be coimmunoprecipitated from rat brain. Synaptic localization of Shank in neurons is inhibited by a GKAP splice variant that lacks the Shank-binding C terminus. In addition to its PDZ domain, Shank contains a proline-rich region that binds to cortactin and a SAM domain that mediates multimerization. Shank may function as a scaffold protein in the PSD, potentially cross-linking NMDA receptor/PSD-95 complexes and coupling them to regulators of the actin cytoskeleton.