PLAKOGLOBIN DOMAINS THAT DEFINE ITS ASSOCIATION WITH THE DESMOSOMAL CADHERINS AND THE CLASSICAL CADHERINS - IDENTIFICATION OF UNIQUE AND SHARED DOMAINS

Two cell-cell junctions, the adherens junction and the desmosome, are prominent in epithelial cells, These junctions are composed of transme mbrane cadherins which interact with cytoplasmic proteins that serve t o link the cadherin to the cytoskeleton. One component of both adheren s junctions and desmosomes is plakoglobin, In the adherens junction pl akoglobin interacts with both the classical cadherin and with alpha-ca tenin, Alpha-catenin in turn interacts with microfilaments. The role p lakoglobin plays in the desmosome is not well understood, Plakoglobin interacts with the desmosomal cadherins, but how and if this mediates interactions with the intermediate filament cytoskeleton is not known, Here we compare the domains of plakoglobin that allow it to associate with the desmosomal cadherins with those involved in interactions wit h the classical cadherins, We show that three sites on plakoglobin are involved in associations with the desmosomal cadherins. A domain near the N terminus is unique to the desmosomal cadherins and overlaps wit h the site that interacts with alpha-catenin, suggesting that there ma y be competition between alpha-catenin and the desmosomal cadherins fo r interactions with plakoglobin, In addition, a central domain is shar ed with regions used by plakoglobin to associate with the classical ca dherins, Finally, a domain near the C terminus is shown to strongly mo dulate the interactions with the desmosomal cadherins, This latter dom ain also contributes to the association of plakoglobin with the classi cal cadherins.