P120-Catenin Regulates Early Trafficking Stages of the N-Cadherin Precursor Complex.

Yulia Komarova,Diana P Wehrendt,Juan M Lázaro Martínez,Carlos O Arregui,Ángela González,Fernando Carmona,Ana E González Wusener

doi:10.1371/journal.pone.0156758

Abstract

It is well established that binding of p120 catenin to the cytoplasmic domain of surface cadherin prevents cadherin endocytosis and degradation, contributing to cell-cell adhesion. In the present work we show that p120 catenin bound to the N-cadherin precursor, contributes to its anterograde movement from the endoplasmic reticulum (ER) to the Golgi complex. In HeLa cells, depletion of p120 expression, or blocking its binding to N-cadherin, increased the accumulation of the precursor in the ER, while it decreased the localization of mature N-cadherin at intercellular junctions. Reconstitution experiments in p120-deficient SW48 cells with all three major isoforms of p120 (1, 3 and 4) had similar capacity to promote the processing of the N-cadherin precursor to the mature form, and its localization at cell-cell junctions. P120 catenin and protein tyrosine phosphatase PTP1B facilitated the recruitment of the N-ethylmaleimide sensitive factor (NSF), an ATPase involved in vesicular trafficking, to the N-cadherin precursor complex. Dominant negative NSF E329Q impaired N-cadherin trafficking, maturation and localization at cell-cell junctions. Our results uncover a new role for p120 catenin bound to the N-cadherin precursor ensuring its trafficking through the biosynthetic pathway towards the cell surface.

Highlights

Cadherins belong to a superfamily of transmembrane cell–cell adhesion molecules which play important roles in development, morphogenesis, and cancer [1, 2]
We show that p120 and protein tyrosine phosphatase protein tyrosine phosphatase 1B (PTP1B) are required for recruiting N-ethylmaleimide sensitive factor (NSF) to the cadherin precursor complex
In a previous study we found that inefficient delivery of N-cadherin to the cell surface correlated with reduced association of p120 catenin to the N-cadherin precursor [22]

Summary

Introduction

Cadherins belong to a superfamily of transmembrane cell–cell adhesion molecules which play important roles in development, morphogenesis, and cancer [1, 2]. The function of cadherins is exerted at the cell surface, where extracellular domains of identical cadherins interact in a homophilic, Ca+2-dependent manner to form adherens junctions between adjacent cells. Proximal and distal regions of cadherin cytosolic domains interact directly with p120 catenin and β-catenin (or its close relative plakoglobin), respectively. Catenins bound to surface cadherins modulate cell-cell adhesion through different mechanisms involving cadherin recycling, stability, and coupling to the actin cytoskeleton. P120 binds to a ~40 amino acids region at the juxtamembrane domain of cadherins, masking clathrin-dependent endocytic motifs [4,5,6,7]. P120 plays a key role as an inhibitor of cadherin turnover

Methods

Results

Conclusion