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

WEHRENDT D. P; CARMONA F; GONZÁLEZ WUSENER A.E; GONZÁLEZ Á; LÁZARO MARTÍNEZ J.M; ARREGUI C. O

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2016

1932-6203

It is well established that binding of p120 catenin to the cytoplasmic domain of surface cadherinprevents cadherin endocytosis and degradation, contributing to cell-cell adhesion. Inthe present work we show that p120 catenin bound to the N-cadherin precursor, contributesto its anterograde movement from the endoplasmic reticulum (ER) to the Golgi complex. InHeLa cells, depletion of p120 expression, or blocking its binding to N-cadherin, increasedthe accumulation of the precursor in the ER, while it decreased the localization of mature Ncadherinat intercellular junctions. Reconstitution experiments in p120-deficient SW48 cellswith all three major isoforms of p120 (1, 3 and 4) had similar capacity to promote the processingof 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 ofthe N-ethylmaleimide sensitive factor (NSF), an ATPase involved in vesicular trafficking, tothe N-cadherin precursor complex. Dominant negative NSF E329Q impaired N-cadherintrafficking, maturation and localization at cell-cell junctions. Our results uncover a new rolefor p120 catenin bound to the N-cadherin precursor ensuring its trafficking through the biosyntheticpathway towards the cell surface.