Ablation of the desmosomal plaque component
plakophilin 1 underlies the autosomal recessive genodermatosis, skin fragility-
ectodermal dysplasia syndrome (OMIM 604536). Skin from affected patients is thickened with increased scale, and there is loss of adhesion between adjacent keratinocytes, which exhibit few small, poorly formed desmosomes. To investigate further the influence of
plakophilin 1 on keratinocyte adhesion and desmosome morphology, we compared
plakophilin 1-deficient keratinocytes (vector controls) with those expressing recombinant
plakophilin 1 introduced by retroviral transduction. We found that
plakophilin 1 increases desmosomal
protein content within the cell rather than enhancing transcriptional levels of desmosomal genes. Re-expression of
plakophilin 1 in null cells retards cell migration but does not alter keratinocyte cell growth. Confluent sheets of
plakophilin 1-deficient keratinocytes display fewer
calcium-independent desmosomes than do
plakophilin 1-deficient keratinocytes expressing recombinant
plakophilin 1 or keratinocytes expressing endogenous
plakophilin 1. In addition electron microscopy studies show that re-expression of
plakophilin 1 affects desmosome size and number. Collectively, these results demonstrate that restoration of
plakophilin 1 function in our culture system influences the transition of desmosomes from a
calcium-dependent to a
calcium-independent state and this correlates with altered keratinocyte migration in response to wounding. Thus,
plakophilin 1 has a key role in increasing desmosomal
protein content, in desmosome assembly, and in regulating cell migration.