Linked Life Data

21156808

Source:http://linkedlifedata.com/resource/pubmed/id/21156808

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-3-1
pubmed:abstractText
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 Ca(2+)-ATPase isoform 2 (SERCA2), a major regulator of intracellular Ca(2+) 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 ? (PKC?), a known regulator of DP-IF association and desmosome assembly, to the plasma membrane by up to 70%. Exogenous activation of PKC? 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 PKC?-dependent mechanism, implicating SERCA2 as a novel regulator of PKC? signaling.
pubmed:grant
http://linkedlifedata.com/resource/pubmed/grant/F30 ES14990, http://linkedlifedata.com/resource/pubmed/grant/R01 AR041836-15, http://linkedlifedata.com/resource/pubmed/grant/R01 AR041836-16, http://linkedlifedata.com/resource/pubmed/grant/R01 AR041836-17, http://linkedlifedata.com/resource/pubmed/grant/R01 AR041836-18, http://linkedlifedata.com/resource/pubmed/grant/R01 AR041836-19, http://linkedlifedata.com/resource/pubmed/grant/R01 AR043380, http://linkedlifedata.com/resource/pubmed/grant/R01 AR043380-11, http://linkedlifedata.com/resource/pubmed/grant/R01 AR043380-12, http://linkedlifedata.com/resource/pubmed/grant/R01 AR043380-13, http://linkedlifedata.com/resource/pubmed/grant/R01 AR043380-14, http://linkedlifedata.com/resource/pubmed/grant/R01 AR043380-15, http://linkedlifedata.com/resource/pubmed/grant/R01 NS057499
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
990-1001
pubmed:dateRevised
2011-5-11
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
The calcium ATPase SERCA2 regulates desmoplakin dynamics and intercellular adhesive strength through modulation of PKCα signaling.
pubmed:affiliation
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural