Biophysical Society Thematic Meeting| Aussois 2019

Biology and Physics Confront Cell-Cell Adhesion

Wednesday Speaker Abstracts

KERATIN ISOTYPES REGULATE DESMOSOME PROTEIN COMPOSITION AND ADHESIVE STRENGTH Thomas M Magin 1 ; Fanny Büchau 1 ; Franziska Vielmuth 2 ; Jens Waschke 2 ; 1 University of Leipzig, Institute of Biology, Div of Cell & Developmental Biology, Leipzig, Germany 2 Ludwig-Maximilians-Universität München, Institute of Anatomy and Cell Biology, Munich, Germany Desmosomes are intercellular junctions that mediate strong cohesion and communication in tissues exposed to high mechanical strain, such as stratified epithelia and the heart. Desmosome adhesive strength depends on the abundance of constituent proteins, their intracellular distribution, posttranslational modifications and associated proteins. The regulation of these parameters during epidermal differentiation, wound healing and pathogenesis remains incompletely understood. Here, we report a novel mechanism by which keratin isotypes regulate desmosome composition and adhesive strength by comparing the impact of K14 and K17 on Dsg1 and Dsg3. Upon Ca2+-induced differentiation, the presence of K17 caused a significant reduction of Dsg1 and a slight increase in Dsg3, whereas K14 promoted the expression of Dsg1. Atomic force microscopy (AFM) and immunofluorescence analysis revealed increased extradesmosomal Dsg1/3 along the plasma membrane and intracellularly. AFM measurements uncovered reduced Dsg3 unbinding forces in the presence of K17. Dsg1 knockdown further weakened adhesion. This indicated that Dsg isotype and abundance contribute to desmosome adhesion. Finally, expression of K17 prevented formation of hyperadhesive desmosomes and delayed expression of terminal differentiation markers such as loricrin and hornerin. Our data unravel the complexity of mechanisms by which keratin isotypes regulate desmosome composition and adhesive strength during keratinocyte differentiation and activation.

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