Expression of the sarco/endoplasmic reticulum calcium ATPase type 2 and 3 isoforms in normal skin and Darier's disease

Abstract

Both SERCA2a and SERCA2b are present in epidermis, although the latter may predominate. The absence of coexpressed SERCA3 in epidermis may explain the localization of DD. Comparable SERCA2 staining intensity in nonlesional DD and control epidermis, even in patients predicted to be haploinsufficient, suggests partial compensation by upregulation of the normal allele. Unknown additional factors may trigger focal lesions by overcoming this compensation. Reduced staining intensity in lesional tissue may be secondary, or may reflect local downregulation of SERCA2 expression predisposing to development of focal lesions.

Role of sarco/endoplasmic reticulum calcium content and calcium ATPase activity in the control of cell growth and proliferation

“…Increasing the cardiac load by aortic banding resulted in faster heart failure in SERCA 2+/-mice than in WT controls [111]. However, in human there is no evidence for cardiac hypertrophy in patients carrying a mutation of the ATP2A2 gene (Darier's disease) [76,122]: up regulation of the normal allele is a possible explanation for the absence of cardiac hypertrophy [121].…”

“…Interestingly, SERCA3 is repressed in highly neoplastic colon cancer cells [8]; consequently, overexpressing SERCA3 in colon cancer to preserve normal ER Ca 2+ levels may be of therapeutic value. SERCA2b expression is decreased in skin disorders related to Darier's disease [11,27,121] and in thyroid cancer [93] but because SERCA2b is the ubiquitous isoform it might be difficult to target precisely.…”

Calcium cycling proteins and heart failure: mechanisms and therapeutics

“…Mice that are haploinsufficient for the SERCA2a gene (Atp2a2) develop accelerated HF progression compared with wild-type controls (48). However, patients with an ATP2A2 mutation and haploinsufficiency (Darier disease) do not have cardiac dysfunction (49). Nevertheless, restoration of normal levels of SERCA2a has been targeted as a novel therapeutic for HF (4).…”

Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca2+ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

“…Mutations in the sarco(endo)plasmic reticulum Ca 2ϩ ATPase (SERCA) isoform 2b (SERCA2b) gene leads to a loss of function, and these mutations have been shown to cause DD (Sakuntabhai et al, 1999). Most physiological systems are able to compensate for the loss of function of SERCA2b, possibly because of expression of other SERCA isoforms within those tissues (Dhitavat et al, 2003;Tavadia et al, 2004). However, of the multiple isoforms of SERCA1, -2, or -3, only SERCA2b is expressed in keratinocytes (Lytton and MacLennan, 1988;Ruiz-Perez et al, 1999).…”