Darier's disease: a calcium-signaling perspective.
Ca(2+) influx evoked across the plasma membrane upon internal store depletion is essential for a myriad of cellular functions including gene expression, cell proliferation, differentiation and even apoptosis. Darier's disease (DD), an autosomal dominant inherited disorder of the skin, arising due to mutations in the isoform 2 of the sarco (endo) plasmic reticulum Ca(2+) ATPase (SERCA2), exemplifies an anomaly of Ca(2+) signaling disturbances. Owing to loss of function mutations in SERCA2, keratinocytes in DD patients have a reduced pool of endoplasmic reticulum (ER) Ca(2+). Importantly, the status of ER Ca(2+) is critical for the activation of a class of plasma membrane Ca(2+) channels referred to as store operated Ca(2+) channels (SOCs). The widely expressed transient receptor potential (TRP) family of channels is proposed to be SOCs. In this review we discuss DD from the viewpoint of Ca(2+) signaling and present a potential role for TRPC1 in the disease pathogenesis.
Pani
B
B
Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, North Dakota, 58202, USA.
Singh
B B
BB
D000818:Animals; D020013:Calcium Signaling; D007644:Darier Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005838:Genotype; D006801:Humans; D010641:Phenotype; D050052:TRPC Cation Channels / Q000378:metabolism
D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1