Two δ-Catenins, Plakophilin 4 and p120, Promote Formation of Distinct Types of Adherens Junctions

Classic cadherins are instrumental for joining cells into tissues by producing cell-cell adhesions known as adherens junctions (AJs). These morphologically diverse structures are tailored to the specific cell sites, type of cells, and particular functions. The mechanism of AJ diversification remains unknown. Here we show that two members of the δ-catenin protein family, p120 and plakophilin 4 (pkp4), which interact with the juxtamembrane intracellular region of classic cadherins, promote distinct types of cadherin clustering thereby contributing to AJ specialization. The type controlled by p120 is driven by interactions between cadherin-associated protein, α-catenin, and actin filaments. This “canonical” clustering mechanism results in formation of AJs that play a major role in overall cell-cell adhesion. The type promoted by pkp4 is driven by an α-catenin-independent cadherin-F-actin interaction. It generates the so-called lateral spot AJs, which apparently function in processes other than cell-cell adhesion. Collectively, our study shows how δ-catenins regulate a balance between different types of AJs in epithelial cells.