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β-catenin is an essential component of two cellular systems: cadherin-based adherens junctions (AJ) and the Wnt signaling pathway. A functional or physical connection between these β-catenin pools has been suggested in previous studies, but not conclusively demonstrated to date. To further examine this intersection, we treated A431 cell colonies with lysophosphatidic acid (LPA), which forces rapid and synchronized dissociation of AJ. A combination of immunostaining, time-lapse microscopy using photoactivatable-GFP-tagged β-catenin, and image analyses indicate that the cadherin-bound pool of β-catenin, internalized together with E-cadherin, accumulates at the perinuclear endocytic recycling compartment (ERC) upon AJ dissociation, and can be translocated into the cell nucleus upon Wnt pathway activation. These results suggest that the ERC may be a site of residence for β-catenin destined to enter the nucleus, and that dissociation of AJ may influence β-catenin levels in the ERC, effectively affecting β-catenin substrate levels available downstream for the Wnt pathway. This intersection provides a mechanism for integrating cell-cell adhesion with Wnt signaling and could be critical in developmental and cancer processes that rely on β-catenin-dependent gene expression.

Cadherin-Bound β-Catenin Feeds into the Wnt Pathway upon Adherens Junctions Dissociation: Evidence for an Intersection between β-Catenin Pools