Consequences of depleted SERCA2-gated calcium stores in the skin

Müller, Eliane J; Caldelari, Reto; Kolly, Carine; Williamson, Lina; Baumann, Dominique; Richard, Gabriele; Jensen, Pamela; Girling, Peter; Delprincipe, Franco; Wyder, Marianne; Balmer, Vreni; Suter, Maja M (2006). Consequences of depleted SERCA2-gated calcium stores in the skin. Journal of Investigative Dermatology, 126(4), pp. 721-31. New York, N.Y.: Nature Publishing 10.1038/sj.jid.5700091

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Sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2) pumps belong to the family of Ca2+-ATPases responsible for the maintenance of calcium in the endoplasmic reticulum. In epidermal keratinocytes, SERCA2-controlled calcium stores are involved in cell cycle exit and onset of terminal differentiation. Hence, their dysfunction was thought to provoke impaired keratinocyte cohesion and hampered terminal differentiation. Here, we assessed cultured keratinocytes and skin biopsies from a canine family with an inherited skin blistering disorder. Cells from lesional and phenotypically normal areas of one of these dogs revealed affected calcium homeostasis due to depleted SERCA2-gated stores. In phenotypically normal patient cells, this defect compromised upregulation of p21(WAF1) and delayed the exit from the cell cycle. Despite this abnormality it failed to impede the terminal differentiation process in the long term but instead coincided with enhanced apoptosis and appearance of chronic wounds, suggestive of secondary mutations. Collectively, these findings provide the first survey on phenotypic consequences of depleted SERCA-gated stores for epidermal homeostasis that explain how depleted SERCA2 calcium stores provoke focal lesions rather than generalized dermatoses, a phenotype highly reminiscent of the human genodermatosis Darier disease.

Item Type:

Journal Article (Original Article)


05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > Equine Clinic

UniBE Contributor:

Müller, Eliane Jasmine; Kolly, Carine; Williamson Ramirez, Lina; Delprincipe, F.; Wyder, Marianne; Balmer, Verena and Suter, Maja




Nature Publishing




Factscience Import

Date Deposited:

04 Oct 2013 14:45

Last Modified:

04 May 2014 23:13

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URI: (FactScience: 896)

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