A Novel Cell-Cell Adhesion System at Adherens Junction

我们已经确定了一种新的细胞-细胞粘附系统，它由nectin和afadin。Nectin是一种免疫球蛋白样粘附分子，afadin是一种与Nectin和肌动蛋白结合的蛋白质，它们广泛表达并定位于粘附连接处。nectin-afadin系统在粘附和紧密连接的正确组织中起重要作用。在本研究项目中，我们研究了nectin-afadin系统的功能和作用方式.粘附和紧密连接的组织。我们已经证明，钙粘蛋白和β-连环蛋白的复合物通过afadin和α-连环蛋白被募集到基于连接蛋白的细胞-细胞连接，ZO-1通过afadin被募集到基于连接蛋白的细胞-细胞连接。这些结果表明，nectin-afadin系统通过募集钙粘蛋白和ZO-1来组织粘附和紧密连接。此外，利用人印戒细胞胃癌细胞系HSC-39细胞，我们已经证明了nectin-afadin和cadherin-catenin系统协同形成粘附连接. mLin-7在粘附连接处的定位。我们已经证明，mLin-7，哺乳动物同源的C。elegans LIN-7通过nectin-afadin系统定位于粘附连接处。哺乳动物mLin-7的功能尚不清楚，而LIN-7参与了C.优雅这些结果表明，nectin-afadin系统决定了某种生长因子受体的定位。

We have identified a novel cell-cell adhesion system, which consists of nectin and afadin. Nectin is an immunoglobulin-like adhesion molecule and afadin is a nectin- and actin filament-binding protein.Nectin and afadin are ubiquitously expressed and localized at adherens junctions. The nectin-afadin system plays an important role in the proper organization of adherens and tight junctions. In the present research project, we have studied the functions and mode of action of the nectin-afadin system.1. Organization of adherens and tight junctions. We have shown that the complex of cadherin and β-catenin is recruited to the nectin-based cell-cell junction through afadin and α-catenin and that ZO-1 is recruited to the nectin-based cell-cell junction through afadin. These results suggest that the nectin-afadin system organizes adherens and tight junctions through the recruitment of cadherin and ZO-1. Moreover, using a human signet ring cell gastric cancer cell line, HSC-39 cells, we have shown that the nectin-afadin and cadherin-catenin systems cooperatively form adherens junctions.2. Localization of mLin-7 at adherens junction. We have shown that mLin-7, the mammalian homologue of C. elegans LIN-7, localizes at adherens junctions through the nectin-afadin system. The function of mammalian mLin-7 is unknown, while LIN-7 is involved in the proper localization of LET-23 receptor tyrosine kinase in C. elegans. These results suggest that the nectin-afadin system determines the localization of a certain growth factor receptor.