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)
Division/Institute:	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) > ISME Equine Clinic Bern > ISME Equine Clinic, Internal medicine
UniBE Contributor:	Müller, Eliane Jasmine, Kolly, Carine, Williamson Ramirez, Lina, Delprincipe, F., Wyder, Marianne, Balmer, Verena, Suter, Maja
ISSN:	0022-202X
Publisher:	Nature Publishing
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:45
Last Modified:	05 Dec 2022 14:14
Publisher DOI:	10.1038/sj.jid.5700091
PubMed ID:	16397524
Web of Science ID:	000238968600007
URI:	https://boris.unibe.ch/id/eprint/18688 (FactScience: 896)