A unique and specific interaction between αT-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 αT-catenin, a novel member of the α-catenin protein family. αT-catenin is expressed predominantly in cardiomyocytes, where it colocalizes with αE-catenin at the intercalated discs. Whether αT- and αE-catenin have specific or synergistic functions remains unknown. In this study we used the yeast two-hybrid approach to identify specific functions of αT-catenin. An interaction between αT-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 αT-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 αT-catenin. By providing an extra link between the cadherin-catenin complex and intermediate filaments, the binding of αT-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.