Activity of the beta-catenin phosphodestruction complex at cell-cell contacts is enhanced by cadherin-based adhesion.

It is well established that cadherin protein levels impact canonical Wnt signaling through binding and sequestering beta-catenin (beta-cat) from T-cell factor family transcription factors. Whether changes in intercellular adhesion can affect beta-cat signaling and the mechanism through which this occurs has remained unresolved. We show that axin, APC2, GSK-3beta and N-terminally phosphorylated forms of beta-cat can localize to cell-cell contacts in a complex that is molecularly distinct from the cadherin-catenin adhesive complex. Nonetheless, cadherins can promote the N-terminal phosphorylation of beta-cat, and cell-cell adhesion increases the turnover of cytosolic beta-cat. Together, these data suggest that cadherin-based cell-cell adhesion limits Wnt signals by promoting the activity of a junction-localized beta-cat phosphodestruction complex, which may be relevant to tissue morphogenesis and cell fate decisions during development.