ANALYSIS OF DESMOSOMAL CADHERIN-ADHESIVE FUNCTION AND STOICHIOMETRY OF DESMOSOMAL CADHERIN-PLAKOGLOBIN COMPLEXES

Desmosomes are intercellular adhesive junctions that associate with th e intermediate filament cytoskeleton, The two major classes of transme mbrane desmosomal glycoproteins, desmogleins and desmocollins, are wid ely considered to function as adhesion molecules, This assumption is b ased in part on their homology to the cadherin family of calcium-depen dent hemophilic adhesion molecules, In addition, autoantibodies from p emphigus patients bind directly to desmoglein family members and are t hought to cause epidermal blistering by inhibiting the function of the se cadherins, To directly test the ability of the desmosomal cadherins to mediate adhesion, desmoglein-1. (Dsg1), desmocollin-2 (Dsc2a) and plakoglobin were expressed in mouse L cell fibroblasts. Similar to cat enin:classical cadherin complexes, plakoglobin:Dsc2a complexes exhibit ed an similar to 1:1 stoichiometry; however, plakoglobin:Dsg1 complexe s exhibited a 6:1 stoichiometry, When L cells expressing the desmosoma l cadherins were tested for the ability to aggregate in suspension, L cells expressing E-cadherin exhibited extensive aggregation, but L cel ls expressing Dsg1 or Dsc2a did not aggregate, In addition, L cells co -expressing Dsg1, Dsc2a, and plakoglobin failed to aggregate. The cyto plasmic domain of E-cadherin is thought to play a central role in the adhesive function of E-cadherin by providing a link to the actin cytos keleton. Therefore, two chimeric cadherins comprising the cytoplasmic domain of E-cadherin and the extracellular domain of either Dsg1 or Ds c2a were expressed in L cells, Both chimeras formed a complex with alp ha- and beta-catenin, Nevertheless, neither of these chimeras supporte d aggregation of L cells when expressed individually or when coexpress ed, These data suggest that the extracellular domains of the desmosoma l cadherins exhibit functional properties distinct from those of the c lassical cadherins, such as E-cadherin.