Assessment of Splice Variant-Specific Functions of Desmocollin 1 in the Skin

Xing Cheng, Kusal Mihindukulasuriya, Zhining Den, Andrew P. Kowalczyk, Cathárine C. Calkins, Akira Ishiko, Atsushi Shimizu, Peter J. Koch

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Desmocollin 1 (Dsc1) is part of a desmosomal cell adhesion receptor formed in terminally differentiating keratinocytes of stratified epithelia. The dsc1 gene encodes two proteins (Dsc1a and Dsc1b) that differ only with respect to their COOH-terminal cytoplasmic amino acid sequences. On the basis of in vitro experiments, it is thought that the Dsc1a variant is essential for assembly of the desmosomal plaque, a structure that connects desmosomes to the intermediate filament cytoskeleton of epithelial cells. We have generated mice that synthesize a truncated Dsc1 receptor that lacks both the Dsc1a- and Dsc1b-specific COOH-terminal domains. This mutant transmembrane receptor, which does not bind the common desmosomal plaque proteins plakoglobin and plakophilin 1, is integrated into functional desmosomes. Interestingly, our mutant mice did not show the epidermal fragility previously observed in dsc1-null mice. This suggests that neither the Dsc1a- nor the Dsc1b-specific COOH-terminal cytoplasmic domain is required for establishing and maintaining desmosomal adhesion. However, a comparison of our mutants with dsc1-null mice suggests that the Dsc1 extracellular domain is necessary to maintain structural integrity of the skin.

Original languageEnglish (US)
Pages (from-to)154-163
Number of pages10
JournalMolecular and cellular biology
Volume24
Issue number1
DOIs
StatePublished - Jan 2004

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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