title: Keratin Isotypes Control Desmosome Stability and Dynamics through PKCα.
abstract: 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 desmosomes is regarded as a 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, on 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 protein kinase C alpha-mediated desmosome disassembly and subsequent destabilization of epithelial sheets. Moreover, our data suggest that K5/K14 sequester protein kinase C alpha in the cytoplasm, whereas K6/K17 or the absence of all keratins enables protein kinase C alpha 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 protein kinase C alpha. Our data show that keratin isotypes differently and specifically regulate wound healing and invasion by modulating intercellular adhesion.
authors.affiliation: Institute of Biology and Translational Center for Regenerative Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Fanny
authors.initials: F
authors.lastname: Loschke
authors.affiliation: Institute of Biology and Translational Center for Regenerative Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Homberg
authors.affiliation: Institute of Biology and Translational Center for Regenerative Medicine, University of Leipzig, Leipzig, Germany. Electronic address: thomas.magin@uni-leipzig.de.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Magin
mesh_terms: D019921:Biotinylation / Q000379:methods; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D002458:Cell Fractionation / Q000379:methods; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D003896:Desmosomes / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D014945:Wound Healing / Q000502:physiology*
chemical_list: C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha