Mechanisms of formation of cell-cell junctions

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We have found a novel cell-cell adhesion system consisting of nectin, an immunoglobulin-like adhesion molecule, and afadin, an F-actin-binding protein. This nectin-afadin system organizes adherens and tight junctions in epithelial cells. During the support from 2003 to 2004, we have studied the functions and mode of action of the nectin-afadin system. The results obtained are as follows :1.A fragment of N-cadherin lacking its extracellular region serves as a dominant negative mutant(DN) and inhibits cell-cell adhesion activity of E-cadherin, but its mode of action remains to be elucidated. We have suggested that N-cadherin DN competitively inhibits the association of the endogenous nectin-afadin system with the endogenous E-cadherin-catenin system and thereby reduces the cell-cell adhesion activity of E-cadherin.2.Nectin is necessary and sufficient for the recruitment of E-cadherin to the nectin-based cell-cell adhesion sites and involved in the formation of E-cadherin-based adherens junctions.3.The nectin-afadin system is involved in dynamic epithelial remodeling during mouse development.4.The contacts between the commissural axons and the floor plate cells are mediated by the hetero-trans-interaction between nectin-1 and nectin-3 and involved in regulation of the trajectory of the commissural axons.