Expression of the sarco/endoplasmic reticulum calcium ATPase type 2 and 3 isoforms in normal skin and Darier's disease

S. Tavadia, K. S. Authi, Malcolm B. Hodgins, C. S. Munro

Research output: Contribution to journalArticle

Abstract

Darier's disease (DD), an autosomal dominant skin disease characterized by multiple discrete or confluent keratoses of teenage or adult onset, is due to heterozygous mutations in ATP2A2, encoding the sarco/endoplasmic reticulum calcium ATPase type 2 (SERCA2). Calcium pumps of the SERCA family play an important role in intracellular calcium homeostasis and signalling, and calcium homeostasis is important in the development of epithelial junctions and cell differentiation. Histologically, DD lesions show suprabasal acantholysis and dyskeratosis, and ultrastructurally lesions show reduced numbers of desmosomes and disruption of desmosomal complexes.1,2 The role of heterozygous mutations in a widely expressed calcium pump in producing a predominantly cutaneous disorder has yet to be elucidated. SERCA2 has two isoforms that differ in their carboxy termini and have distinct tissue expression patterns: SERCA2a occurs mainly in cardiac and skeletal muscle, whereas SERCA2b is ubiquitously expressed. High levels of expression of both SERCA2a and SERCA2b have been shown by Western blotting in cultured normal human keratinocytes.3 Ruiz-Perez et al. showed that cultured keratinocytes and fibroblasts are labelled by anti-SERCA2a and anti-SERCA2b antibodies and that SERCA2b is expressed in epidermis of normal adult skin sections.4 In a pilot immunohistochemistry study of normal human epidermis and epidermis from a patient with DD, we found both SERCA2a and SERCA2b to be expressed.5 Recently, using an antibody recognizing both SERCA2 isoforms, Sheridan et al. demonstrated that SERCA2 was expressed in normal human skin and mucosa and in skin from six patients with DD.6 There are two other proteins in the human SERCA family. Expression of SERCA type 1 is confined to muscle, but SERCA type 3 (SERCA3) is coexpressed with SERCA2b in many tissues. SERCA3 may thus provide some redundancy in calcium signalling,7 but its expression in skin has not been reported. To investigate the role of tissue-specific patterns of SERCA isoform expression in the pathogenesis of DD we have studied patterns of SERCA2 and SERCA3 expression in skin, and have quantified epidermal SERCA2a and SERCA2b staining intensity in biopsies from normal subjects and patients with DD.

Original languageEnglish
JournalBritish Journal of Dermatology
Publication statusPublished - 1 Aug 2004

Keywords

  • epidermis
  • immunohistochemistry
  • calcium ATPase
  • Darier's disease

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