title: P120-Catenin Regulates Early Trafficking Stages of the N-Cadherin Precursor Complex.
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.
authors.affiliation: Instituto de Investigaciones Biotecnológicas, (IIB-INTECH), Universidad de San Martín, San Martín, Argentina.
authors.forename: Diana P
authors.initials: DP
authors.lastname: Wehrendt
authors.affiliation: Instituto de Investigaciones Biotecnológicas, (IIB-INTECH), Universidad de San Martín, San Martín, Argentina.
authors.forename: Fernando
authors.initials: F
authors.lastname: Carmona
authors.affiliation: Instituto de Investigaciones Biotecnológicas, (IIB-INTECH), Universidad de San Martín, San Martín, Argentina.
authors.forename: Ana E
authors.initials: AE
authors.lastname: González Wusener
authors.affiliation: Instituto de Investigaciones Biotecnológicas, (IIB-INTECH), Universidad de San Martín, San Martín, Argentina.
authors.forename: Ángela
authors.initials: Á
authors.lastname: González
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CABA, Argentina.
authors.forename: Juan M Lázaro
authors.initials: JM
authors.lastname: Martínez
authors.affiliation: Instituto de Investigaciones Biotecnológicas, (IIB-INTECH), Universidad de San Martín, San Martín, Argentina.
authors.forename: Carlos O
authors.initials: CO
authors.lastname: Arregui
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D051177:Catenins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D055571:Secretory Pathway; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; D052066:N-Ethylmaleimide-Sensitive Proteins; D000095002:Delta Catenin; C000722347:CTNND1 protein, human