Beschreibung:
<jats:p>Desmosomes are patch‐like cell contact structures that are essential for the integrity of the epidermis by providing adhesive strength between keratinocytes. The core is organized of transmembrane proteins of the desmosomal cadherin family, which bind to their counterparts on the adjacent cell via their extracellular domain and are linked intracellularly to the keratin filament network by adapter proteins such as plakoglobin (Pg) and desmoplakin (Dsp). Since in the severe skin blistering disease pemphigus autoantibodies bind to desmosomal cadherins and induce loss of keratinocyte cohesion at least in part via p38MAPK activation and cause depletion of desmosomal components, we evaluated the roles of Pg and Dsp in p38MAPK‐dependent loss of cell adhesion. siRNA‐mediated silencing of either Pg or Dsp protein expression reduced cohesion of cultured human keratinocytes in dissociation assays. However, Pg but not Dsp silencing induced activation of p38MAPK. Accordingly, cell dissociation was blunted by p38MAPK inhibition under conditions of reduced Pg expression only. Interestingly, keratin filament retraction, a hallmark of pemphigus, was prominent under diminished Pg levels, an effect prevented by p38MAPK inhibition. Our data indicate that p38MAPK‐dependent keratin filament collapse is involved in loss of cell adhesion in response to Pg but not Dsp depletion.</jats:p>