Desmoglein 2 contributes to cell cohesion dependent on the desmosomal cadherin expression pattern

Abstract

Desmoglein (Dsg) 2 is the most widespread isoform of the desmosomal cadherin protein family, of which four desmoglein (Dsg1–4) and three desmocollin (Dsc1–3) isoforms are expressed in keratinocytes. In the blistering skin disease pemphigus vulgaris (PV), Dsg3 is a target of autoantibodies indicating a central role for Dsg3 in keratinocyte cohesion. In contrast, for Dsg2 the role for keratinocyte cohesion has not been defined yet. We demonstrated the importance of Dsg2 for intestinal epithelial cells by incubation of Caco2 cells with a monoclonal Dsg2 antibody (Dsg2 mAb) which reduced cell integrity in a dissociation assay. However, Dsg2 mAb, in contrast to AK23, a pathogenic PV antibody targeting Dsg3, did not reduce cell cohesion in keratinocytes (HaCaT). To confirm that both antibodies are potent to bind their target protein we detected both antibodies’ heavy chains by Western blot analysis. Additionally both antibodies led to a decrease in the number of binding events of their corresponding recombinant Dsg target protein probed by atomic force microscopy (AFM). In contrast to another colorectal adenocarcinoma cell line (HT‐29), siRNA‐mediated silencing of Dsg2 in HaCaT cells reduced cell cohesion only under conditions of increased shear. These results indicate that Dsg2 contributes differently to cell cohesion dependent on the expression pattern of desmosomal cadherin family isoforms. DFG SFB487, SP1300–1