Two δ-catenins, plakophilin 4 and p120, promote formation of distinct types of adherens junctions

TL;DR

This study shows how two δ-catenins help form different types of cell adhesions, contributing to the diversity of adherens junctions in tissues.

Contribution

The paper reveals that p120 and plakophilin 4 promote distinct cadherin clustering modes, leading to different adherens junction types.

Findings

p120 promotes α-catenin-dependent clustering for apical and basal adherens junctions.

pkp4 promotes α-catenin-independent clustering for lateral adherens junctions.

δ-catenins regulate AJ assembly pathways, contributing to AJ diversity.

Abstract

Classic cadherins form diverse cell–cell adhesions, AJs, yet the basis of this diversity remains unclear. We show that two δ-catenins, p120 and plakophilin-4, promote distinct cadherin clustering modes, α-catenin–dependent and α-catenin–independent, respectfully, thereby generating different types of AJs. Thus, δ-catenins regulate alternative AJ assembly pathways contributing to AJ diversity.

Classical cadherins are instrumental for connecting cells into tissues by forming adherens junctions (AJs), a structurally diverse class of cell–cell adhesions tailored to specific membrane domains, cell types, and particular functions. The mechanisms that underlie the AJ diversification remain unknown. Here, we show that two δ-catenin family members, p120 and plakophilin 4 (pkp4), which bind the intracellular region of classical cadherins, promote distinct modes of cadherin clustering, thereby contributing to AJ specialization. The mode promoted by p120 is driven by interactions between cadherin-associated protein, α-catenin, and actin filaments. This “canonical” clustering mechanism generates apical and basal AJs that play a major role in overall cell–cell adhesion. The mode promoted by pkp4 is driven by an α-catenin–independent mechanism. It generates lateral AJs, which apparently function in processes other than cell–cell adhesion. Collectively, our findings show that δ-catenins regulate the balance between different AJ assembly pathways, thereby contributing to AJ diversification.

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