Recycling of E-cadherin: A potential mechanism for regulating cadherin dynamics

E-Cadherin plays critical roles in many aspects of cell adhesion, epithelia l development, and the establishment and maintenance of epithelial polarity . The fate of E-cadherin once it is delivered to the basolateral cell surfa ce, and the mechanisms which govern its participation in adherens junctions , are not well understood. Using surface biotinylation and recycling assays , we observed that some of the cell surface E-cadherin is actively internal ized and is then recycled back to the plasma membrane. The pool of E-cadher in undergoing endocytosis and recycling was markedly increased in cells wit hout stable cell-cell contacts, i.e., in preconfluent cells and after cell contacts were disrupted by depletion of extracellular Ca2+, suggesting that endocytic trafficking of E-cadherin is regulated by cell-cell contact. The reformation of cell junctions after replacement of Ca2+ was then found to be inhibited when recycling of endocytosed E-cadherin was disrupted by bafi lomycin treatment. The endocytosis and recycling of E-cadherin and of the t ransferrin receptor were similarly inhibited by potassium depletion and by bafilomycin treatment, and both proteins were accumulated in intracellular compartments by an 18 degrees C temperature block, suggesting that endocyto sis may occur via a clathrin-mediated pathway. We conclude that a pool of s urface E-cadherin is constantly trafficked through an endocytic, recycling pathway and that this may provide a mechanism for regulating the availabili ty of E-cadherin for junction formation in development, tissue remodeling, and tumorigenesis.