A Novel Cell-Cell Adhesion System at Adherens Junction

我们发现了一种新的细胞-细胞黏附系统，该黏附系统由Nextin和afadin组成。Nectin是一种免疫球蛋白样黏附分子，afadin是一种Nectin和肌动蛋白细丝结合蛋白。Nectin和afadin广泛表达和定位于黏附连接。Nectin-afadin系统在粘附物和紧密连接的正确组织中起着重要作用。在本研究项目中，我们对Nectin-afadin系统的功能和作用模式进行了研究。粘连和紧密连接的组织。我们已经证明，钙粘素和β-连环蛋白的复合体通过Fafadin和α-连环蛋白被募集到基于Nectin的细胞-细胞连接，而ZO-1通过Fafadin被招募到基于Nectin的细胞-细胞连接。这些结果表明，Nectin-afadin系统通过募集钙粘附素和ZO-1来组织黏附和紧密连接。此外，利用人类印戒细胞系HSC-39细胞，我们已经证明了粘附素-afadin和钙粘附素-连接素系统协同形成粘连连接。Mlin-7基因在黏附连接的定位。我们已经证明，线虫LIN-7的哺乳动物同源物Mlin-7通过Nectin-afadin系统定位于粘连连接。哺乳动物Mlin-7的功能尚不清楚，而Lin-7参与线虫LET-23受体酪氨酸激酶的正确定位。这些结果表明，Nextin-afadin系统决定了某个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.