Send to:

Choose Destination
See comment in PubMed Commons below
J Invest Dermatol. 2006 Apr;126(4):702-3.

The focal nature of Darier's disease lesions: calcium pumps, stress, and mutation?

Author information

  • 1Institute for Cell and Molecular Sciences, Queen Mary, University of London, London, United Kingdom.


Haploinsufficiency of the ATP2A2 gene product, SERCA2, underlies most cases of Darier's disease. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase isoform 2 (SERCA2) is an intracellular Ca2+ pump that replenishes ER Ca2+, and it seems likely that the disease manifests in stress-induced lesions because SERCA levels become limiting as extra demands are made on the pump in times of stress. However, Müller and colleagues (2006) present a radical new proposal invoking somatic mutation as the basis for Darier lesions. Using a novel animal model for depleted keratinocyte SERCA-gated Ca2+ stores, the authors show that keratinocytes from Darier-like lesions retain their distinctive phenotype after culture, suggesting heritable defects. Mechanistically linking stress, calcium levels, mutation, and disease pathogenesis is complicated, and the proposal is likely to be controversial. However, recent reports of age- and stress-dependent tumor formation in the mouse model for SERCA2 haploinsufficiency (ATP2A2 heterozygous mouse) support the proposal that deficiency in SERCA-gated ER Ca2+ replenishment may be linked to mutation accumulation.

Comment on

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Write to the Help Desk