Darier's disease: from dyskeratosis to endoplasmic reticulum calcium ATPase deficiency.
The skin is the body's largest organ and has an essential barrier protective function against physical, chemical, and pathogen aggressions and prevents fluid loss. The outer layer of the skin, known as the epidermis, plays a key role in this protection, through a tightly regulated differentiation programme from basal keratinocytes to the stratum corneum at the skin surface. During this process, keratinocytes from the base of the epidermis undergo major morphological and functional changes during their migration through the spinous and granular layers, to become terminally differentiated corneocytes which will be shed from the skin's surface. The role of extracellular Ca2+ in cell-to-cell adhesion and in epidermal differentiation was known to be important, but the identification of the sarco/endoplasmic reticulum Ca2+ transport ATPase (ATP2A2) as the defective gene in a rare genetic skin disease known as Darier's disease, came as a surprise and shed light on the key role of Ca2+ signaling in the homeostasis of the epidermis.
Hovnanian
Alain
A
Department of Medical Genetics, INSERM U563 and University Paul Sabatier, Purpan Hospital, Place du Dr Baylac, 31059 Toulouse, Cedex 03, France. alain.hovnanian@toulouse.inserm.fr
D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D000252:Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D007644:Darier Disease / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D007642:Keratosis / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation; D014176:Protein Biosynthesis; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D000252:Calcium-Transporting ATPases; D002118:Calcium