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Lookup NU author(s): Dr Victor Ruiz-Perez,
Professor Jonathan Rees,
Professor Tom Strachan
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Darier’s disease (DD) has recently been shown to be due to mutations in ATP2A2 (SERCA2; Sakuntabhai et al. Nature Genet 21:271–277, 1999), a widely expressed ATPase which pumps cytoplasmic calcium into the endoplasmic reticulum for use in calcium signalling. Intriguingly, mice hemizygous for a null mutation in SERCA2 exhibit impaired cardiac performance (Periasamy et al. J Biol Chem 274:2556–25, 199). ATP2A2 has 21 exons and two alternatively spliced products, SERCA2a and SERCA2b, which differ only in the C-terminal domain; SERCA2a is the predominant isoform in heart. Although both isoforms were identified in keratinocyte cDNA, expression in skin has not been studied directly. To examine SERCA2 expression in skin, we have used antibodies recognising the distinct C-terminal domains of SERCA2a and 2b to study normal human skin and cultured cells (gift of Dr F Wuytack, Leuven, Belgium; Wuytack et al. Biochem J 257:117–123, 1989). In cultured human keratinocytes and fibroblasts both 2a and 2b-specific antibodies showed clear cytoplasmic immunostaining. On sections of adult skin 2a isoform-specific staining was difficult to distinguish from background, but 2b isoform-specific staining showed clear positivity in epidermal structures including interfollicular epidermis, pilosebaceous units and sweat glands. Little staining was observed in the dermis. Using SSCP screening and/or direct sequencing, we have identified mutations in over 40 pedigrees of DD, which occur in 19 of 21 exons and include nonsense and splice site mutations predicted to affect expression of both isoforms of SERCA2, in addition to missense mutations which might have specific effects. SERCA2b appears to be the predominant isoform in epidermis, but it is unlikely that the apparent absence of cardiac phenotype in DD is related to the pattern of isoform expression.
Author(s): Todd C; Strachan T; Ruiz-Perez VL; Rees JL; Carter SA; Munro CS; Smith M
Publication type: Conference Proceedings (inc. Abstract)
Publication status: Published
Conference Name: Annual Meeting for the European Society for Dermatological Research
Year of Conference: 1999
Publisher: Nature Publishing Group
Notes: Meeting Abstract: 003
Library holdings: Search Newcastle University Library for this item
Series Title: The Journal of Investigative Dermatology