STRUCTURE OF DSG1, THE BOVINE DESMOSOMAL CADHERIN GENE ENCODING THE PEMPHIGUS FOLIACEUS ANTIGEN - EVIDENCE OF POLYMORPHISM

The cadherin superfamily of calcium-dependent cell-cell adhesion and r ecognition proteins can be categorized into a number of subsets on the basis of the distinct cytoplasmic sequences of their members. Current ly these families include classical cadherins, desmogleins, desmocolli ns, protocadherins, and the products of the Drosophila genes FAT and D achsous. Dsg1, the prototype of the desmoglein family, is a major comp onent of epidermal desmosomes and the antigenic target of antibodies f ound in the sera of patients with the blistering disease, pemphigus fo liaceus. In this study, we determined the organization of the bovine D SG1 gene. This gene consists of 15 exons distributed over >37.5 kiloba ses of genomic DNA. A comparison of DSG1 with genes encoding classical cadherins revealed a striking conservation of exon boundaries in regi ons encoding the ectodomain and to a more limited extent among those e ncoding the cytoplasmic domain. Polymorphism was found in a sequence o f DSG1 encoding protein proximal to the external face of the plasma me mbrane. This region is topologically equivalent to a domain of classic al cadherins that harbors epitopes recognized by adhesion-disrupting a ntibodies. We discuss these results with regard to the evolution of th e cadherin superfamily and their implications for the definition of pe mphigus epitopes.