title: A unique and specific interaction between alphaT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs.
abstract: Alpha-catenins play key functional roles in cadherin-catenin cell-cell adhesion complexes. We previously reported on alphaT-catenin, a novel member of the alpha-catenin protein family. alphaT-catenin is expressed predominantly in cardiomyocytes, where it colocalizes with alphaE-catenin at the intercalated discs. Whether alphaT- and alphaE-catenin have specific or synergistic functions remains unknown. In this study we used the yeast two-hybrid approach to identify specific functions of alphaT-catenin. An interaction between alphaT-catenin and plakophilins was observed and subsequently confirmed by co-immunoprecipitation and colocalization. Interaction with the amino-terminal part of plakophilins appeared to be specific for the central ;adhesion-modulation' domain of alphaT-catenin. In addition, we showed, by immuno-electron microscopy, that desmosomal proteins in the heart localize not only to the desmosomes in the intercalated discs but also at adhering junctions with hybrid composition. We found that in the latter junctions, endogenous plakophilin-2 colocalizes with alphaT-catenin. By providing an extra link between the cadherin-catenin complex and intermediate filaments, the binding of alphaT-catenin to plakophilin-2 is proposed to be a means of modulating and strengthening cell-cell adhesion between cardiac muscle cells. This could explain the devastating effect of plakophilin-2 mutations on cell junction stability in intercalated discs, which lead to cardiac muscle malfunction.
authors.affiliation: Department for Molecular Biomedical Research, VIB, Ghent University, B-9052 Ghent, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Goossens
authors.forename: Barbara
authors.initials: B
authors.lastname: Janssens
authors.forename: Stefan
authors.initials: S
authors.lastname: Bonné
authors.forename: Riet
authors.initials: R
authors.lastname: De Rycke
authors.forename: Filip
authors.initials: F
authors.lastname: Braet
authors.forename: Jolanda
authors.initials: J
authors.lastname: van Hengel
authors.forename: Frans
authors.initials: F
authors.lastname: van Roy
mesh_terms: D000818:Animals; D003893:Desmin / Q000235:genetics / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D016253:Microscopy, Immunoelectron; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000648:ultrastructure; D051191:Plakophilins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C441963:CTNNA3 protein, human; D003893:Desmin; D051191:Plakophilins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D051178:alpha Catenin