The amino- and carboxyl-terminal tails of beta-catenin reduce its affinityfor desmoglein 2

Beta-catenin and plakoglobin are members of the armadillo family of protein s and were first identified as components of intercellular adhering junctio ns. In the adherens junction beta-catenin and plakoglobin serve to link cla ssical cadherins to the actin-based cytoskeleton. In the desmosome plakoglo bin links the desmosomal cadherins, the desmogleins and the desmocollins, t o the intermediate filament cytoskeleton, beta-catenin is not a component o f the desmosome. Previously we have shown that the central armadillo repeat region of plakoglobin is the site for desmosomal cadherin binding. We hypo thesized that the unique amino- and/or carboxyl-terminal ends of beta-caten in may regulate its exclusion from the desmosomal plaque. To test this hypo thesis we used chimeras between beta-catenin and plakoglobin to identify do main(s) that modulate association with desmoglein 2. Chimeric constructs, e ach capable of associating with classical cadherins, were assayed for assoc iation with the desmosomal cadherin desmoglein 2, Addition of either the N- or C-terminal tail of beta-catenin to the armadillo repeats of plakoglobin did not interfere with desmoglein 2 association. However, when both beta-c atenin amino terminus and carboxyl terminus were added to the plakoglobin a rmadillo repeats, association with desmoglein 2 was diminished. Removal of the first 26 amino acids from this construct restored association, We show evidence for direct protein-protein interactions between the amino- and car boxyl-terminal tails of beta-catenin and propose that a sequence in the fir st 26 amino acids of beta-catenin along with its carboxyl-terminal tail dec rease its affinity for desmoglein and prevent its inclusion in the desmosom e.