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The calcium ATPase SERCA2 regulates desmoplakin dynamics and intercellular adhesive strength through modulation of PKCα signaling.
- Source :
-
FASEB Journal . Mar2011, Vol. 25 Issue 3, p990-1001. 12p. - Publication Year :
- 2011
-
Abstract
- Darier's disease (DD) is an inherited autosomal-dominant skin disorder characterized histologically by loss of adhesion between keratinocytes. DD is typically caused by mutations in sarcoendoplasmic reticulum Ca2+-ATPase isoform 2 (SERCA2), a major regulator of intracellular C2+ homeostasis in the skin. However, a defined role for SERCA2 in regulating intercellular adhesion remains poorly understood. We found that diminution of SERCA2 function by pharmacological inhibition or siRNA silencing in multiple human epidermal-derived cell lines was sufficient to disrupt desmosome assembly and weaken intercellular adhesive strength. Specifically, SERCA2-deficient cells exhibited up to a 60% reduction in border translocation of desmoplakin (DP), the desmosomal cytolinker protein necessary for intermediate filament (IF) anchorage to sites of robust cell-cell adhesion. In addition, loss of SERCA2 impaired the membrane translocation of protein kinase C α (PKCα), a known regulator of DP-IF association and desmosome assembly, to the plasma membrane by up to 70%. Exogenous activation of PKCα in SERCA2-deficient cells was sufficient to rescue the defective DP localization, desmosome assembly, and intercellular adhesive strength to levels comparable to controls. Our findings indicate that SERCA2-deficiency is sufficient to impede desmosome assembly and weaken intercellular adhesive strength via a PKCα-dependent mechanism, implicating SERCA2 as a novel regulator of PKCα signaling. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08926638
- Volume :
- 25
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- FASEB Journal
- Publication Type :
- Academic Journal
- Accession number :
- 65150801
- Full Text :
- https://doi.org/10.1096/fj.10-163261