Binding to cadherins antagonizes the signaling activity of β-catenin during axis formation in Xenopus

Abstract

β-Catenin, a cytoplasmic protein known for its association with cadherin cell adhesion molecules, is also part of a signaling cascade involved in embryonic patterning processes such as the determination of the dorsoventral axis in Xenopus and determination of segment polarity in Drosophila. Previous studies suggest that increased cytoplasmic levels of β-catenin correlate with signaling, raising questions about the need for interaction with cadherins in this process. We have tested the role of the β-catenin-cadherin interaction in axis formation. Using β-catenin deletion mutants, we demonstrate that significant binding to cadherins can be eliminated without affecting the signaling activity. Also, depletion of the soluble, cytosolic pool of β-catenin by binding to overexpressed C-cadherin completely inhibited β-catenin-inducing activity. We conclude that binding to cadherins is not required for β-catenin signaling, and therefore the signaling function of β-catenin is independent of its role in cell adhesion. Moreover, because β-catenin signaling is antagonized by binding to cadherins, we suggest that cadherins can act as regulators of the intracellular β-catenin signaling pathway.