p120 catenin recruits NSF to the N-cadherin precursor and promotes its processing and trafficking

DIANA P. WEHRENDT, FERNANDO CARMONA AND CARLOS O. ARREGUI

Rosario

Congreso; 50 Reunión Anual de SAIB; 2014

SAIB

N-cadherin is synthesized in endoplasmic reticulum (ER)-bound ribosomes as a precursor protein (pro-N-cad) and processed at the trans-Golgi network to generate a mature protein that carries its function at the cell surface. Binding of p120-catenin to N-cadherin occurs at the ER, and is critical for N-cadherin stability at the cell surface. Here we examined the role of p120 to promote the traffic of pro-N-cad through the biosynthetic pathway. We show that by preventing p120 binding to pro-N-cad, either by mutation of the p120-binding site or by p120 depletion, the precursor accumulates, while mature N-cadherin decreases. Confocal microscopy analysis reveals that pro-N-cad accumulation occurs at the ER. Reconstitution experiments in p120-deficient SW48 cells show that expression of all three major isoforms of p120 (p120 1A, 3A and 4A) have similar capacity to promote the processing of pro-N-cad and its localization at cell-cell junctions. We found that N-ethylmaleimide sensitive factor (NSF), an essential regulator of vesicular trafficking, is recruited by p120 to the pro-N-cad complex. Functional NSF is required for N-cad trafficking, maturation and localization at cell-cell junctions. Our results suggest a novel role of p120 in the processing of pro-N-cad and its trafficking to the cell surface, likely through the recruitment of NSF to the complex. Supported by CONICET and ANPCyT.