WNT-1 MODULATES CELL-CELL ADHESION IN MAMMALIAN-CELLS BY STABILIZING BETA-CATENIN BINDING TO THE CELL-ADHESION PROTEIN CADHERIN

Wnt-1 homologs have been identified in invertebrates and vertebrates a nd play important roles in cellular differentiation and organization. In Drosophila, the products of the segment polarity genes wingless (th e Wnt-1 homolog) and armadillo participate in a signal transduction pa thway important for cellular boundary formation in embryonic developme nt, but functional interactions between the proteins are unknown. We h ave examined Wnt-1 function in mammalian cells in which armadillo (bet a-catenin and plakoglobin) is known to bind to and regulate cadherin c ell adhesion proteins. We show that Wnt-1 expression resuits in the ac cumulation of beta-catenin and plakoglobin. In addition, binding of be ta-catenin to the cell adhesion protein, cadherin, is stabilized, resu lting in a concomitant increase in the strength of calcium-dependent c ell-cell adhesion. Thus, a consequence of the functional interaction b etween Wnt-1 and armadillo family members is the strengthening of cell -cell adhesion, which may lead to the specification of cellular bounda ries.