Neural cell adhesion molecule (NCAM) association with PKCbeta2 via betaI spectrin is implicated in NCAM-mediated neurite outgrowth.
Neural cell adhesion molecule (NCAM) association with PKCbeta2 via betaI spectrin is implicated in NCAM-mediated neurite outgrowth.
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DOI：
10.1083/jcb.200303020
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发表时间：
2003-05-12
期刊：
影响因子：
--
通讯作者：
Schachner M
中科院分区：
文献类型：
--
作者：
Leshchyns'ka I;Sytnyk V;Morrow JS;Schachner M
在海马神经元和转染的CHO细胞中，神经细胞粘附分子（NCAM）120、NCAM 140和NCAM 180与βI血影蛋白形成Triton X-100不溶性复合物。异聚血影蛋白（αIβI）与NCAM 180的胞内结构域结合，分离的血影蛋白亚基与NCAM 180和NCAM 140结合，包含第二和第三血影蛋白重复序列（βI2-3）的βI血影蛋白片段也是如此。在NCAM 120转染的细胞中，βI血影蛋白主要在脂筏中检测到。用甲基-β-环糊精处理细胞破坏NCAM 120-血影蛋白复合物，暗示脂筏作为连接NCAM 120和血影蛋白的平台。NCAM 140/NCAM 180-βI血影蛋白复合物不依赖于筏的完整性，并且位于筏和无筏膜结构域中。PKCβ2与NCAM 140/NCAM 180和血影蛋白形成不溶于洗涤剂的复合物。NCAM的激活增强了NCAM 140/NCAM 180-血影蛋白-PKC β2复合物的形成，并导致其重新分布至脂筏。该复合物被显性负性βI2-3的表达破坏，这损害了血影蛋白与NCAM的结合，暗示血影蛋白是PKCβ2与NCAM 140或NCAM 180之间的桥梁。PKCβ2向NCAM-血影蛋白复合物的再分布也被特异性成纤维细胞生长因子受体抑制剂阻断。此外，βI2-3转染抑制NCAM诱导的神经突生长，表明NCAM-血影蛋白-PKCβ2复合物的形成是NCAM介导的神经突生长所必需的。
In hippocampal neurons and transfected CHO cells, neural cell adhesion molecule (NCAM) 120, NCAM140, and NCAM180 form Triton X-100–insoluble complexes with βI spectrin. Heteromeric spectrin (αIβI) binds to the intracellular domain of NCAM180, and isolated spectrin subunits bind to both NCAM180 and NCAM140, as does the βI spectrin fragment encompassing second and third spectrin repeats (βI2–3). In NCAM120-transfected cells, βI spectrin is detectable predominantly in lipid rafts. Treatment of cells with methyl-β-cyclodextrin disrupts the NCAM120–spectrin complex, implicating lipid rafts as a platform linking NCAM120 and spectrin. NCAM140/NCAM180–βI spectrin complexes do not depend on raft integrity and are located both in rafts and raft-free membrane domains. PKCβ2 forms detergent-insoluble complexes with NCAM140/NCAM180 and spectrin. Activation of NCAM enhances the formation of NCAM140/NCAM180–spectrin–PKCβ2 complexes and results in their redistribution to lipid rafts. The complex is disrupted by the expression of dominant-negative βI2–3, which impairs binding of spectrin to NCAM, implicating spectrin as the bridge between PKCβ2 and NCAM140 or NCAM180. Redistribution of PKCβ2 to NCAM–spectrin complexes is also blocked by a specific fibroblast growth factor receptor inhibitor. Furthermore, transfection with βI2–3 inhibits NCAM-induced neurite outgrowth, showing that formation of the NCAM–spectrin–PKCβ2 complex is necessary for NCAM-mediated neurite outgrowth.
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