Functions and mode of action of novel regulatory systems for cell adhesion and motility

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We have found a novel regulatory system for cell adhesion. This system consists of nectin and afadin. Nectin is an immunoglobulin-like cell adhesion molecule, and afadin is an F-aotin-binding protein that connects nectin to the actin cytoskeleton.The nectin-afadin system organizes adherens and tight jjunctions in epithelial cells.We have also found a novel regulatory system for cell motility. This system consists of frabin and Cdc42 small G protein. Frabin is an F-actin-blnding protein that activates Cdc42. During this support from2000-to 2001, we have studied the functions and mode of action of these nectin-afadin and frabin-Cdc42 systems. The results obtained are as follows :(1) In epithelial cells, the nectin-afadin system recruits the cadherin-catenin and JAM-ZO-lsystems to nectin-based cell-cell adhesion sites. In neurons, the nectin-afadinsystemis localized at synapses and involved information of synapses. In testis, the nectin-afadin system is involved in formation of Sertoli-spermatid junctions and essential for spermatid morphogenesis.(2) Frabin associates with specific actin and membrane structures and activates not only Cdc42 and but also Rac small G protein in the vicinity of these structures, eventually to leading to cell motility. The F-actin-binding activity of frabin cooperatively functions with the Cdc42-activating activity in cell motility.