Regulation of epithelial cell adhesion and repulsion: role of endocytic recycling.

A proper balance between cell adhesion and repulsion is essential for cellular morphogenesis during epithelial-mesenchymal transition and mesenchymal-epithelial transition. A number of ligand-receptor pairs including hepatocyte growth factor/scatter factor-Met and semaphorin-plexin are known to control this balance through the complex intracellular signaling pathways. Cell adhesion to other cells and extracellular matrix (ECM) is mediated by cell adhesion molecules (CAMs) and ECM receptors, respectively, which are associated with cytoskeleton through a variety of plaque proteins strengthening and/or weakening adhesion activities. Cell repulsion requires the downregulation of cell adhesion and the extensive changes in cytoskeletal dynamics. The endocytic recycling of CAMs and ECM receptors has recently emerged as an important mechanism to control the balance between cell adhesion and repulsion. Molecule interacting with CasL (MICAL) family proteins are originally identified as a plaque protein associated with ECM receptors integrins and implicated in semaphorin-plexin dependent repulsive axon guidance. We have recently shown that MICAL family protein JRAB/MICAL-L2 functions as an effector protein for Rab family small G protein Rab13 and regulates the endocytic recycling of tight junctional CAM occludin and controls the adhesion and repulsion of epithelial cells.