Regulation of the assembly and adhesion activity of E-cadherin by nectin and afadin for the formation of adherens junctions in Madin-Darby canine kidney cells
Regulation of the assembly and adhesion activity of E-cadherin by nectin and afadin for the formation of adherens junctions in Madin-Darby canine kidney cells
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DOI：
10.1074/jbc.m510070200
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发表时间：
2006-02-24
影响因子：
4.8
通讯作者：
Takai, Y
中科院分区：
文献类型：
--
作者：
Sato, T;Fujita, N;Takai, Y
钙非依赖性免疫球蛋白样分子Nectin首先形成细胞间的黏附，然后在基于Nectin的细胞间黏附部位聚集钙粘素，形成黏附连接(AJs)。Afadin是一种连接Nectin和肌动蛋白细胞骨架的粘连蛋白和肌动蛋白纤维结合蛋白。在此，我们研究了Nextin和afadin在培养的MDCK细胞AJs形成中的作用和作用方式。与p120(CTN)、β-连环蛋白和α-连环蛋白结合的上皮钙粘附素在基于连结蛋白的细胞-细胞黏附部位的反式相互作用不依赖于afadin。然而，组装的E-钙粘附素表现出较弱的细胞间黏附活性，可能是非反式相互作用的形式。这种组装是由IQGAP1依赖的肌动蛋白细胞骨架介导的，该骨架是由CDC42和Rac小G蛋白组成的，这些小G蛋白通过c-Src和Rap1小G蛋白的反式相互作用而激活，而不依赖于afadin。然而，Rap1与afadin结合，然后该Rap1-afadin复合体与非反式相互作用的E-钙粘蛋白相关的p120(CTN)相互作用，从而导致E-钙粘素的反式相互作用。因此，Nectin通过afadin、Nectin信号转导和p120(CTN)调节E-钙粘素的组装和细胞间黏附活性，从而在Madin-Darby犬肾细胞中形成AJs。
The Ca2+-independent immunoglobulin-like molecule nectin first forms cell-cell adhesion and then assembles cadherin at nectin-based cell-cell adhesion sites, resulting in the formation of adherens junctions (AJs). Afadin is a nectin- and actin filament-binding protein that connects nectin to the actin cytoskeleton. Here, we studied the roles and modes of action of nectin and afadin in the formation of AJs in cultured MDCK cells. The trans-interaction of nectin assembled E-cadherin, which associated with p120(ctn), beta-catenin, and alpha-catenin, at the nectin- based cell-cell adhesion sites in an afadin-independent manner. However, the assembled E-cadherin showed weak cell-cell adhesion activity and might be the non-trans-interacting form. This assembly was mediated by the IQGAP1-dependent actin cytoskeleton, which was organized by Cdc42 and Rac small G proteins that were activated by the action of trans-interacting nectin through c-Src and Rap1 small G protein in an afadin-independent manner. However, Rap1 bound to afadin, and this Rap1-afadin complex then interacted with p120(ctn) associated with non-trans-interacting E-cadherin, thereby causing the trans-interaction of E-cadherin. Thus, nectin regulates the assembly and cell-cell adhesion activity of E-cadherin through afadin, nectin signaling, and p120(ctn) for the formation of AJs in Madin-Darby canine kidney cells.