NEW INSIGHTS INTO THE REGULATION OF E-CADHERIN DISTRIBUTION BY ENDOCYTOSIS

Homeostasis of adherens junctions is achieved through complex regulatory mechanisms. The junctions are highly dynamic in contact establishment, in remodeling events during development, and during processes involving a loss of adhesion like epithelial mesenchyme transition. It appeared recently that they are also dynamically renewed in mature, steady-state adhesions. Indeed, maintenance of a steady state must be integrated into a tight control of force equilibrium between a cell and its neighbors. Therefore, it appears that E-cadherin dynamics allows to respond constantly to various biochemical and mechanical stimuli and to regulate the movement and shape of junctions in active remodeling processes. E-cadherin dynamics is mediated through several mechanisms (diffusion, trafficking) in function of the biological system. In mature junctions, membrane E-cadherin is quickly renewed by endocytosis in many cell types. E-cadherin endocytosis shows a complex regulation, depending on small G proteins, ubiquitination, cleavage events, actomyosin cytoskeleton, and other trans molecules in adherens junctions. It is modulated by growth factor stimulations and physical factors. Consequently, E-cadherin endocytosis tightly controls a number of functional processes: cell movements, junction maintenance, cell sorting, and polarity. Misregulated E-cadherin endocytosis is involved in many diseases, from cancerous processes to organogenesis defects.