A Novel Cell-Cell Adhesion System at Adherens Junction

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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.