Molecular control mechanism of the cadherin-mediated cell-cell adhesion

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The E-cadherin-catenin complex regulates calcium ion-dependent cell-cell adhesion and is localized to the basal-lateral membrane of polarized epithelial cells. Little is known about mechanisms of complex assembly or inrtracellular trafficking, or how these processes might ultimately regulate adhesion functions of the complex at the cell surface. Deletions of the region of the cytoplasmic domain of E-cadherin involved in beta-catenin-binding resulted in delivery of <10% of these proteins to cell surfaces. An E-cadherin construct uncoupled for beta-catenin-binding by amino acid substitutions in the region was also localized intracellularly. Thus, beta-catenin binding to the cytoplasmic domain of E-cadherin seemed to be required for the efficient transport to the cell surface. Contrary to this observation, >90% of E-cadherin lacking its entire cytoplasmic domain was detected on the surface of cells. To define the region of the E-cadherin cytoplasmic domain responsible for the intracellular accumulation of the beta-catenin-uncoupled E-cadherin constructs, we made a series of deletion constructs. Removal of the membrane-proximal region resulted in the cell surface expression of the constructs. Uncoupling p120-binding, however, did not change the distribution of the constructs.