Darier's disease: A calcium-signaling perspective

Ca²⁺ 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 Ca²⁺ signaling disturbances. Owing to loss of function mutations in SERCA2, keratinocytes in DD patients have a reduced pool of endoplasmic reticulum (ER) Ca²⁺. Importantly, the status of ER Ca²⁺ is critical for the activation of a class of plasma membrane Ca²⁺ channels referred to as store operated Ca²⁺ 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 Ca²⁺ signaling and present a potential role for TRPC1 in the disease pathogenesis.