E-cadherin is a member of the cadherin family of Ca2+-dependent cell-cell adhesion molecules. p120-Catenin and δ-catenin are known to bind to similar juxtamembrane regions of E-cadherin, and p120-catenin is known to stabilize E-cadherin. However, the function of competition between p120-catenin and δ-catenin for the E-cadherin has not been fully explained. In this report, we show that cells overexpressing δ-catenin contain less p120-catenin than control cells at cell-cell interface and that this causes the re-localization of p120-catenin from the plasma membrane to the cytosol. We show that successful binding by one to E-cadherin adversely affects the stability of the other.

Accumulated evidence suggests that aberrant regulation of δ-catenin leads to pathological consequences such as mental retardation and cognitive dysfunction. This study revealed that 14-3-3ɛ/ζ stabilizes δ-catenin, with different binding regions involved in the interaction. Furthermore, the specific inhibition of the interaction of 14-3-3 with δ-catenin reduced levels of δ-catenin and significantly impaired the capacity of δ-catenin to induce dendritic branching in both NIH3T3 fibroblasts and primary hippocampal neurons. However, the S1094A δ-catenin mutant, which cannot interact with 14-3-3ζ, still retained the capability of inducing dendrogenesis. Taken together, these results elucidate the underlying events that regulate the stability of δ-catenin and δ-catenin-induced dendrogenesis.