Assembly of desmosomal cadherins into desmosomes is isoform dependent

Desmosomes are intercellular adhesive junctions that exhibit cell- and diff erentiation-specific differences in their molecular composition. In complex epithelia, desmosomes contain multiple representatives of the desmosomal c adherin family, which includes three desmogleins and three desmocollins, Ru les governing the assembly of desmosomal cadherin isoforms into desmosomes of different cell types are unknown, Here we compared the assembly properti es of desmoglein 2 (Dsg2) and desmocollin 2 (Dsc2), which are widely expres sed, with Dsg1 and Dsc1, which are expressed in the differentiated layers o f complex epithelia, by introducing myc-tagged forms into simple and squamo us epithelial cells that do not express Dsg1 or Dsc1, Dsc2,myc and Dsg2,myc assembled efficiently into desmosomes in every cell type in spite of signi ficant shifts in the stoichiometric relationship between desmogleins and de smocollins, In contrast, Dsc1a,myc, Dsc1b,myc, and Dsg1,myc did not stably incorporate into desmosomes in any line. Coexpression of Dsc1a.myc or Dsc1b .myc and Dsg1.myc did not lead to their colocalization and failed to enhanc e incorporation of either cadherin into desmosomes. Dsg1.myc, but not Dsc1a , Dsc1b, disrupted desmosome assembly ill a cell-type-specific manner, and disruption correlated with the recruitment of Dsg1.myc, but not Dsc1a or Ds c1b, into a Triton-insoluble pool. The plakoglobin:E-cadherin ratio decreas ed in Dsg1-expressing cells with disrupted desmosomes, but a decrease was a lso observed in a Dsc1a line. Thus, a modest reduction of plakoglobin assoc iated with E-cadherin is apparently trot sufficient to disrupt desmosome as sembly. Our results demonstrate that desmosome assembly tolerates large shi fts in cadherin stoichiometry, but is sensitive to isoform-specific differe nces exhibited by desmogleins and desmocollins,.