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Adducin modulates intercellular keratinocyte adhesion
Author(s) -
Roetzer Vera,
Waschke Jens,
Spindler Volker
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.650.15
Subject(s) - rhoa , microbiology and biotechnology , actin cytoskeleton , chemistry , keratinocyte , focal adhesion , cell adhesion , actin , desmoglein , cytoskeleton , biology , phosphorylation , cadherin , cell , in vitro , biochemistry , signal transduction
Adducin is an actin‐binding protein necessary for proper assembly of the cortical actin belt. Although regulation of the membrane cytoskeleton by adducin is well established, a role for cell adhesion has not been investigated so far. We found that siRNA‐mediated silencing of adducin reduced desmoglein (Dsg) 3 protein levels and decreased intercellular adhesion of human keratinocytes in dispase‐based dissociation assays. Previous data indicated that the loss of keratinocyte cohesion by Dsg autoantibodies in the blistering skin disease pemphigus is paralleled by pronounced actin reorganization and blocked by RhoA activation. Since cortical actin polymerization is required for Rho GTPase‐mediated strengthening of cell adhesion, we studied the role of adducin in this context. AK23, a pathogenic Dsg3 antibody from a pemphigus mouse model, resulted in rapid adducin phosphorylation at Serin726, a residue important for regulation of adducin activity. AK23‐mediated cell dissociation was blocked by RhoA activation via Y. pseudotuberculosis cytotoxic necrotizing factor y (CNFy). However, under conditions of adducin silencing or after expression of a phosphorylation‐deficient adducin mutant, the protective effect of CNFy was inhibited. These data demonstrate that adducin is necessary for proper intercellular adhesion and suggest an involvement in the protective effect of RhoA in pemphigus vulgaris.