Association of Caspr/paranodin with tumour suppressor schwannomin/merlin and β1 integrin in the central nervous system
Association of Caspr/paranodin with tumour suppressor schwannomin/merlin and β1 integrin in the central nervous system
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DOI：
10.1046/j.1471-4159.2003.01503.x
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发表时间：
2003-01-01
影响因子：
4.7
通讯作者：
Girault, JA
中科院分区：
文献类型：
--
作者：
Denisenko-Nehrbass, N;Goutebroze, L;Girault, JA
CASPR/paranodin是结旁轴突连接的重要神经元成分，与Conactin/F3相关。它的短胞内区含有一个保守的基序(GNP基序)，能够与蛋白4.1结构域[FERM结构域(Four point one，Ezrin，Radioxin，moesin)]结合。Schwannomin/Merlin是一种肿瘤抑制因子，在许多细胞类型中都有表达，包括在神经元中表达，但其功能和伴侣仍未得到很好的描述。我们发现，在谷胱甘肽S转移酶下拉实验中和在转染的COS-7细胞中，神经鞘蛋白的FERM结构域与Paranodin GNP基序结合。这两种蛋白质在脑提取液中免疫共沉淀。此外，在转基因细胞和脑匀浆中，Paranodin和Schwannomin与整合素β(1)相关。Paranodin的存在增加了整合素β(1)与神经鞘蛋白或其N末端结构域之间的联系，表明这些蛋白质之间的相互作用是相互依赖的。在表现出严重髓鞘异常和结旁连接缺陷的小鼠中，副神经节蛋白、神经鞘蛋白和整合素β(1)之间的相互作用发生了深刻的变化。我们的结果表明，神经鞘蛋白和整合素β(1)可能与中枢神经系统中的Paranodin有关。由于整合素β(1)和雪旺诺明似乎不富含偏执素，它们在这些区域可能是偏执素的次要伙伴，和/或在其他位置与偏执素有关。
Caspr/paranodin is an essential neuronal component of paranodal axoglial junctions, associated with contactin/F3. Its short intracellular domain contains a conserved motif (GNP motif) capable of binding protein 4.1 domains [FERM domains (four point one, ezrin, radixin, moesin)]. Schwannomin/merlin is a tumour suppressor expressed in many cell types, including in neurons, the function and partners of which are still poorly characterized. We show that the FERM domain of schwannomin binds to the paranodin GNP motif in glutathione S-transferase (GST)-pull down assays and in transfected COS-7 cells. The two proteins co-immunoprecipitated in brain extracts. In addition, paranodin and schwannomin were associated with integrin beta(1) in transfected cells and in brain homogenates. The presence of paranodin increased the association between integrin beta(1) and schwannomin or its N-terminal domain, suggesting that the interactions between these proteins are interdependent. In jimpy mutant mice, which display a severe dysmyelination with deficient paranodal junctions, the interactions between paranodin, schwannomin and integrin beta(1) were profoundly altered. Our results show that schwannomin and integrin beta(1) can be associated with paranodin in the central nervous system. Since integrin beta(1) and schwannomin do not appear to be enriched in paranodes they may be quantitatively minor partners of paranodin in these regions and/or be associated with paranodin at other locations.