Premium
Differential contribution of desmoglein 2 and 3 to cell adhesion and intracellular signaling in keratinocytes
Author(s) -
Hartlieb Eva,
Spindler Volker,
Waschke Jens
Publication year - 2012
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.26.1_supplement.833.2
Subject(s) - desmoglein , desmoglein 3 , keratinocyte , microbiology and biotechnology , desmosome , cadherin , cell adhesion , pemphigus vulgaris , chemistry , cell adhesion molecule , adhesion , immunology , biology , cell , antibody , autoantibody , in vitro , biochemistry , organic chemistry
Desmosomes provide intercellular adhesive strength required for integrity of epithelial and some non‐epithelial tissues. Within the epidermis, the cadherin‐type adhesion molecules desmoglein (Dsg) 1–4 and desmocollin 1–3 build the core of desmosomes. In keratinocytes, several isoforms of these proteins are co‐expressed, however the contribution of specific isoforms to overall cell cohesion is unclear. In this study, we investigated the roles of Dsg2 and Dsg3, the latter of which is known to be essential for keratinocyte adhesion based on its autoantibody‐induced loss of function in the autoimmune blistering skin disease pemphigus vulgaris (PV). The pathogenic PV antibody AK23 targeting the Dsg3 adhesive domain led to profound loss of cell cohesion. In contrast, a Dsg2 antibody also interfering with Dsg2 adhesion had no effect. SiRNA‐mediated knockdown of Dsg3 induced loss of cell cohesion accompanied by activation of p38MAPK. Both effects were not detectable after Dsg2 knockdown. Interestingly, subsequent incubation with AK23 led to drastically enhanced keratinocyte cell dissociation and p38MAPK activation in Dsg2 knockdown cells. These experiments indicate that specific desmosomal cadherins contribute differently to cell adhesion and intracellular signaling in human keratinocytes. Furthermore, an additive mechanism of Dsg2 and Dsg3 for cell adhesion is likely. DFG SFB487