Regulation of E-cadherin endocytosis by nectin through afadin, Rap1, and p120ctn
Regulation of E-cadherin endocytosis by nectin through afadin, Rap1, and p120ctn
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DOI：
10.1074/jbc.m414447200
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发表时间：
2005-06-24
影响因子：
4.8
通讯作者：
Takai, Y
中科院分区：
文献类型：
--
作者：
Hoshino, T;Sakisaka, T;Takai, Y
黏附连接是上皮细胞中一种主要的细胞-细胞黏附结构，由两个主要的细胞-细胞黏附分子E-钙粘蛋白和粘附素形成。我们先前已经证明，Nextin首先形成细胞-细胞黏附，然后将非反式相互作用的E-钙粘附素招募到基于Nextin的细胞-细胞黏附部位，在那里逐渐反式相互作用，最终形成AJs。我们在这里研究了反式相互作用的胶凝素对非反式相互作用的E-钙粘素内吞作用的影响。能够与afadin结合的反式相互作用的Nextin，但不能与afadin结合的反式相互作用的Nectin突变体，抑制了完整细胞中非反式相互作用的E-钙粘素内吞。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。通过无细胞实验对Nectin-afadin系统作用方式的研究表明，Fafadin与反式相互作用的Nectin结合的Rap1结合，与p120(CTN)相互作用，并加强p120ctn与E-钙粘素的结合，最终减少非反式相互作用的E-钙粘素内吞。不结合Rap1的Afadin在这方面不活跃。这些结果表明，反式相互作用的粘附素通过afadin、Rap1和p120ctn抑制非反式相互作用的E-钙粘附素的内吞作用，从而进一步将非反式相互作用的E-钙粘附素聚集到基于Nextin的细胞-细胞黏附部位，以形成AJs。
Adherens junctions (AJs) are a major cell-cell adhesion structure in epithelial cells that are formed by two major cell-cell adhesion molecules, E-cadherin and nectin. We have previously shown that nectin first forms cell-cell adhesion and then recruits non-trans-interacting E-cadherin to the nectin-based cell-cell adhesion sites, which gradually trans-interact there, eventually forming AJs. We have examined here the effect of trans-interacting nectin on non-trans-interacting E-cadherin endocytosis. Trans-interacting nectin capable of associating with afadin, but not trans-interacting nectin mutant incapable of associating with afadin, inhibited non-trans-interacting E-cadherin endocytosis in intact cells. Afadin is a nectin- and actin filament-binding protein that connects nectin to the actin cytoskeleton. Studies on the mode of action of the nectin- afadin system using cell-free assay revealed that afadin associated with nectin bound Rap1 activated by trans-interacting nectin, interacted with p120(ctn), and strengthened the binding of p120ctn to E-cadherin, eventually reducing non-trans-interacting E-cadherin endocytosis. Afadin, which did not bind Rap1, was inactive in this capacity. These results indicate that trans-interacting nectin inhibits non-trans-interacting E-cadherin endocytosis through afadin, Rap1, and p120ctn and thereby further accumulates non-trans-interacting E-cadherin to the nectin-based cell-cell adhesion sites for the formation of AJs.