Keratin Isotypes Control Desmosome Stability and Dynamics through PKCα

Expression and interaction of desmosomal components and keratins provide stable cell cohesion and protect the epidermis against various types of stress. The differentiation-specific isotype composition of the keratin cytoskeleton and of desmosomes is regarded as major determinant of adhesive strength. In support, wound healing is characterized by a transient decrease in desmosomal adhesion accompanied by increased expression of keratins K6/K16/K17 at the expense of K1/K10. The significance of altered keratin expression for desmosomal composition and adhesion remains incompletely understood at a mechanistic and functional level. Here, we investigated the respective contribution of K5/K14 or K6/K17 to desmosome adhesion, upon their stable re-expression in keratinocytes lacking all keratins. This revealed that K5/K14 filaments support stable desmosomes, whereas 'wound healing' keratins K6/K17 induce elevated PKCα-mediated desmosome disassembly and subsequent destabilization of epithelial sheets. Moreover, our data suggest that K5/K14 sequester PKCα in the cytoplasm, whereas K6/K17 or absence of all keratins enables PKCα-translocation to the plasma membrane and induction of desmosome disassembly. Gain- and loss-of-function experiments support a major role of K5 in desmosome stability control via PKCα. Our data show that keratin isotypes differently and specifically regulate wound healing and invasion by modulating intercellular adhesion.Journal of Investigative Dermatology accepted article preview online, 12 October 2015. doi:10.1038/jid.2015.403.