Calcium Pumps and Keratinocytes: Lessons From Darier's Disease and Hailey-Hailey Disease

J. Dhitavat; R.J. Fairclough; A. Hovnanian; S.M. Burge


The British Journal of Dermatology. 2004;150(5) 

In This Article


Clearer understanding of the molecular basis of Darier's disease and Hailey-Hailey disease has provided compelling evidence that Ca2+- and Mn2+-ATPases play a key role in the assembly of desmosomes in the epidermis. Defective cell adhesion may be secondary to abnormalities in the recruitment, folding, sorting or trafficking of desmosomal proteins or the stabilization of the junctions through links with the cytoskeleton. Abnormalities in the sorting of desmoplakin play an important part in the pathogenesis of acantholysis and dyskeratosis in Darier's disease and the role of plaque proteins should be investigated further in Hailey-Hailey disease. Further investigation may also shed light on clinical phenomena such as photoexacerbation, aggravation by heat and, in Darier's disease, lithium-induced deterioration. The impact of treatments such as corticosteroids or retinoids on pump activity also deserves further investigation.

Research into intracellular Ca2+ and Mn2+ homeostasis, intracellular signalling, the trafficking of desmosomal proteins and the assembly of desmosomes in these diseases will provide more valuable insights into the regulation of adhesion, differentiation and proliferation in normal epidermis. This work may also have an impact on the management of skin disorders in which keratinocyte adhesion, differentiation and/or proliferation are abnormal.

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