Dissociation of intra- and extracellular domains of desmosomal cadherins and E-cadherin in Hailey-Hailey disease and Darier's disease

Megumi Hakuno, H. Shimizu, M. Akiyama, M. Amagai, J. K. Wahl, M. J. Wheelock, T. Nishikawa

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62 Citations (Scopus)

Abstract

In order to clarify the pathomechanism of acantholysis in Hailey-Hailey disease (HHD) and Darier's disease (DD), the distribution of desmosomal and adherens junction-associated proteins was studied in the skin of patients with HHD (n = 4) and DD (n = 3). Domain-specific antibodies were used to determine the cellular localization of the desmosomal transmembrane glycoproteins (desmogleins 1 and 3 and desmocollin), desmosomal plaque proteins (desmoplakin, plakophilin and plakoglobin) and adherens junction- associated proteins (E-cadherin, α-catenin, β-catenin and actin). A significant difference in staining patterns between intra- and extracellular domains of desmosomal cadherins and E-cadherin was demonstrated in acantholytic cells in both HHD and DD, but not in those in pemphigus vulgaris and pemphigus foliaceus samples used as controls. In acantholytic cells in HHD and DD, antibodies against attachment plaque proteins and intracellular epitopes of desmosomal cadherins exhibited diffuse cytoplasmic staining, whereas markedly reduced staining was observed with antibodies against extracellular epitopes of the desmogleins. Similarly, membrane staining of an intracellular epitope of E-cadherin was preserved, while immunoreactivity of an extracellular epitope of E-cadherin was destroyed. While the DD gene has been identified as ATP2A2, the gene for HHD has not been clarified. The dissociation of intra- and extracellular domains of desmosomal cadherin and E-cadherin is characteristic of the acantholytic cells in HHD and DD, and not of pemphigus. This common phenomenon in HHD and DD might be closely related to the pathophysiological mechanisms in both conditions.

Original languageEnglish
Pages (from-to)702-711
Number of pages10
JournalBritish Journal of Dermatology
Volume142
Issue number4
DOIs
Publication statusPublished - 2000 May 9
Externally publishedYes

Keywords

  • Adherens junction
  • Cell adhesion molecule
  • Desmocollin
  • Desmoglein
  • Desmosome
  • Familial benign chronic pemphigus

ASJC Scopus subject areas

  • Dermatology

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