title: α-Catenin contributes to the strength of E-cadherin-p120 interactions.
abstract: Cadherin-catenin interactions play an important role in cadherin-mediated adhesion. Here we present strong evidence that in the cadherin-catenin complex α-catenin contributes to the binding strength of another catenin, p120, to the same complex. Specifically, we found that a β-catenin-uncoupled cadherin mutant interacts much more weakly with p120 than its full-size counterpart and that it is rapidly endocytosed from the surface of A-431 cells. We also showed that p120 overexpression stabilizes this mutant on the cell surface. Examination of the α-catenin-deficient MDA-MB-468 cells and their derivates in which α-catenin was reintroduced showed that α-catenin reinforces E-cadherin-p120 association. Finally, a cross-linking analysis of the cadherin-catenin complex indicated that a large loop located in the middle of the p120 arm-repeat domain is in close spatial vicinity to the amino-terminal VH1 domain of α-catenin. The six amino acid-long extension of this loop, caused by an alternative splicing, weakens p120 binding to cadherin. The data suggest that α-catenin-p120 contact within the cadherin-catenin complex can regulate cadherin trafficking.
authors.affiliation: Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Regina B
authors.initials: RB
authors.lastname: Troyanovsky
authors.forename: Jörg
authors.initials: J
authors.lastname: Klingelhöfer
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Troyanovsky
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D051177:Catenins / Q000096:biosynthesis / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D009154:Mutation; D011485:Protein Binding; D021381:Protein Transport; D015398:Signal Transduction; D051178:alpha Catenin / Q000172:deficiency / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D051178:alpha Catenin; D051176:beta Catenin; D000095002:Delta Catenin