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Ca 2+ signalling is important for loss of keratinocyte adhesion in pemphigus vulgaris
Author(s) -
Schmitt Thomas,
Waschke Jens
Publication year - 2020
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.2020.34.s1.02870
Subject(s) - pemphigus vulgaris , desmoglein 3 , phospholipase c , microbiology and biotechnology , desmoglein , pemphigus , keratinocyte , chemistry , phospholipase , endoplasmic reticulum , desmosome , adhesion , biology , immunology , cadherin , cell , autoantibody , antibody , biochemistry , signal transduction , organic chemistry , in vitro , enzyme
Pemphigus vulgaris (PV) is a severe blistering skin disease caused by autoantibodies (PV‐IgG) against desmogleins (Dsg)1 and 3. Ca 2+ release in response to PV‐IgG has been reported. However, its contribution to loss of keratinocyte adhesion is largely unknown. Phosphatidylinositol‐4‐kinase‐a (PI4K) and phospholipase‐C‐γ1 (PLC) release inositol‐3‐phos‐phate (IP3) activating the IP3‐receptor (IP3R) and thereby causing Ca 2+ flux from the endoplasmic reticulum (ER) into the cytoplasm. Low Ca 2+ in the ER activates the Ca 2+ release‐activated‐channel (CRAC) to replenish the Ca 2+ store. Inhibitors against PI4K, PLC, IP3R or CRAC were applied under conditions under which they effectively blocked Ca 2+ influx. All inhibitors ameliorated PV‐IgG‐induced alterations of Dsg1 and Dsg3 localization, keratin filament retraction and loss of cell adhesion in dissociation assays. Inhibition of PLC completely abolished PV‐IgG‐induced and also ameliorated AK23‐mediated loss of adhesion. These data demonstrate that Ca 2+ signalling is important for loss of cell adhesion in PV but independent from antibodies against Dsg3 supporting the hypothesis that autoantibodies engage different signalling mechanisms to reduce cell adhesion. Support or Funding Information Funded by the DFGCa‐dependendent interacellular signalling in pemphigus vulgaris. Black arrows indicate calcium‐flux.