DESMOSOMES ARE REGULATED BY PROTEIN-KINASE-C IN PRIMARY RAT EPITHELIAL-CELLS

In the present study, we addressed the possible relevance of protein k inase C (PKC) in the regulation of intracytoplasmic desmosome assembly . Treatment of cultured rat Lingual and epidermal keratinocytes with a potent and highly selective PKC inhibitor (GF109203X) induced an incr ease in granular labelling for major desmosomal proteins, desmoplakins , desmoglein and plakoglobin, both intracellularly and at the cell sur face. This was associated with the formation of ultrastructurally reco gnizable desmosomes deep in the cytoplasm and increase in intercellula r desmosome number. In contrast, PKC activation upon short exposure to 12-O-tetradecanoylphorbol 13-acetate (TPA) resulted in altered cell m orphology, loss of intercellular contact and accumulation of desmosoma l proteins in the juxtanuclear zone. On the other hand, PKC depletion by long term TPA treatment re-established cell-cell contact, where des mosomal markers were exclusively redistributed. Taken together, these results suggest that inhibition of PKC is required for intracytoplasmi c as well as intercellular desmosome assembly, whereas its activation may regulate disassembly process.