DESMOSOMAL CADHERIN BINDING DOMAINS OF PLAKOGLOBIN

Plakoglobin is a major component of both desmosomes and adherens junct ions. At these sites it binds to the cytoplasmic domains of cadherin c ell-cell adhesion proteins and regulates their adhesive and cytoskelet al binding functions. Plakoglobin also forms distinct cytosolic protei n complexes that function in pathways of tumor suppression and cell fa te determination. Recent studies in Xenopus suggest that cadherins inh ibit the signaling functions of plakoglobin presumably by sequestering this protein at the membrane and depleting its cytosolic pool. To und erstand the reciprocal regulation between desmosomal cadherins (desmog lein and desmocollin) and plakoglobin, we have sought to identify the binding domains involved in the formation of these protein complexes. Plakoglobin comprises 13 central repeats flanked by amino-terminal and carboxyl-terminal domains. Our results show that repeats 1-4 are invo lved in binding desmoglein-1. In contrast, the interaction of plakoglo bin with desmocollin-1a is sensitive to deletion of either end of the central repeat domain. The binding sites for two adherens junction com ponents, alpha-catenin and classical cadherins, overlap these sites. C ompetition among these proteins for binding sites on plakoglobin may t herefore account for the distinct composition of adherens junctions an d desmosomes.