Bidirectional regulation of desmosome hyperadhesion by keratin isotypes and desmosomal components.

Autor: Büchau F; Institute of Biology, Division of Cell and Developmental Biology, University of Leipzig, Philipp-Rosenthal-Straße 55, 04103, Leipzig, Germany. fanny.buechau@uni-leipzig.de., Vielmuth F; Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Munich, Germany., Waschke J; Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Munich, Germany., Magin TM; Institute of Biology, Division of Cell and Developmental Biology, University of Leipzig, Philipp-Rosenthal-Straße 55, 04103, Leipzig, Germany.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2022 Apr 05; Vol. 79 (5), pp. 223. Date of Electronic Publication: 2022 Apr 05.
DOI: 10.1007/s00018-022-04244-y
Abstrakt: Desmosomes are intercellular junctions which mediate cohesion and communication in tissues exposed to mechanical strain by tethering the intermediate filament cytoskeleton to the plasma membrane. While mature desmosomes are characterized by a hyperadhesive, Ca 2+ -independent state, they transiently loose this state during wound healing, pathogenesis and tissue regeneration. The mechanisms controlling the hyperadhesive state remain incompletely understood. Here, we show that upon Ca 2+ -induced keratinocyte differentiation, expression of keratin 17 (K17) prevents the formation of stable and hyperadhesive desmosomes, accompanied by a significant reduction of desmoplakin (DP), plakophilin-1 (PKP1), desmoglein-1 (Dsg1) and -3 (Dsg3) at intercellular cell borders. Atomic force microscopy revealed that both increased binding strength of desmoglein-3 molecules and amount of desmoglein-3 oligomers, known hallmarks of hyperadhesion, were reduced in K17- compared to K14-expressing cells. Importantly, overexpression of Dsg3 or DPII enhanced their localization at intercellular cell borders and increased the formation of Dsg3 oligomers, resulting in stable, hyperadhesive desmosomes despite the presence of K17. Notably, PKP1 was enriched in these desmosomes. Quantitative image analysis revealed that DPII overexpression contributed to desmosome hyperadhesion by increasing the abundance of K5/K17-positive keratin filaments in the proximity of desmosomes enriched in desmoglein-3. Thus, our data show that hyperadhesion can result from recruitment of keratin isotypes K5/K17 to desmosomes or from enhanced expression of DP and Dsg3 irrespective of keratin composition. The notion that hyperadhesive desmosomes failed to form in the absence of keratins underscores the essential role of keratins and suggest bidirectional control mechanisms at several levels.
(© 2022. The Author(s).)
Databáze: MEDLINE
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