Differential structural properties and expression patterns suggest functional significance for multiple mouse desmoglein 1 isoforms

Donna Brennan, Ying Hu, Ana Kljuic, Yoo Won Choi, Sohaila Joubeh, Marisa Bashkin, James K Wahl, Andrzej Fertala, Leena Pulkkinen, Jouni Uitto, Angela M. Christiano, Andrey Panteleyev, Mỹ G. Mahoney

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The four isoforms of desmosomal cadherin desmogleins (Dsg1-4) are expressed in epithelial tissues in a differentiation-specific manner. Extensive sequencing of the human genome has revealed only one copy of the Dsg1 gene. However, we recently cloned two novel additional mouse Dsg1 genes, Dsg1-β and -γ, which flank the original Dsg1-α on chromosome 18. Sequence conservation between the Dsg1 isoforms diverged significantly at exon 11, particularly in the region that encodes for the extracellular anchoring (EA) domains. Computational analysis revealed very low hydrophilic potential of the Dsg1-γ EA compared with the corresponding sequences of Dsg1-α and -β, suggesting that the Dsg1-γ EA domain may have a stronger affinity to the cell membrane. We generated antibodies using synthetic peptides or recombinant proteins localized within the EA domains. These antibodies were tested for their specificity and were then used to demonstrate expression of Dsg1 isoforms in various tissues. In the epidermis, all Dsg1 isoforms were differentially expressed in the differentiating cell layers. In the hair follicle, all Dsg1 isoforms were present throughout the entire process of its development and cycling but the expression of Dsg1 isoforms is subject to significant hair cycle-dependent changes. Dsg1-β and -γ, but not Dsg1-α, were detected in the sebaceous gland epithelium and the stratified epithelium of the stomach. Finally, Dsg1-α and Dsg1-β, but not Dsg1-γ, are proteolytically cleaved by exfoliative toxin A. These results suggest that the developmental complexity of mouse tissues, including skin and hair, may play a significant role in the evolutionary driving force to maintain multiple Dsg1 genes in mouse.

Original languageEnglish (US)
Pages (from-to)434-449
Number of pages16
JournalDifferentiation
Volume72
Issue number8
DOIs
Publication statusPublished - Oct 2004

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Keywords

  • Cadherins
  • Cell adhesion
  • Desmoglein
  • Desmosome
  • Differentiation
  • Hair follicle

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology
  • Cancer Research

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