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First published online 2 July 2003
doi: 10.1242/jcs.00636
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Research Article |
1 Department of Cell and Molecular Pathology, St John's Institute of
Dermatology, Guy's, King's and St Thomas' School of Medicine, London, UK
2 Richard Dimbleby/Cancer Research UK Department of Cancer Research, Guy's,
King's and St Thomas' School of Medicine, London, UK
3 Centre for Cutaneous Research, St Bartholomew's and the Royal London School of
Medicine and Dentistry, London, UK
* Author for correspondence (e-mail: andrew.south{at}kcl.ac.uk)
Accepted 28 April 2003
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.
Key words: Desmosomes, Keratinocyte, Calcium, Plakophilin 1, Skin
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