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Mol Biol Cell. 2018 Sep 15;29(19):2317-2325. doi: 10.1091/mbc.E17-06-0387. Epub 2018 Jul 25.

Transition of responsive mechanosensitive elements from focal adhesions to adherens junctions on epithelial differentiation.

Author information

1
Forschungszentrum Jülich, Institute of Complex Systems, ICS-7: Biomechanics, 52428 Jülich, Germany.
2
Department of Dermatology, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
3
Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, 30625 Hannover, Germany.

Abstract

The skin's epidermis is a multilayered epithelial tissue and the first line of defense against mechanical stress. Its barrier function depends on an integrated assembly and reorganization of cell-matrix and cell-cell junctions in the basal layer and on different intercellular junctions in suprabasal layers. However, how mechanical stress is recognized and which adhesive and cytoskeletal components are involved are poorly understood. Here, we subjected keratinocytes to cyclic stress in the presence or absence of intercellular junctions. Both states not only recognized but also responded to strain by reorienting actin filaments perpendicular to the applied force. Using different keratinocyte mutant strains that altered the mechanical link of the actin cytoskeleton to either cell-matrix or cell-cell junctions, we show that not only focal adhesions but also adherens junctions function as mechanosensitive elements in response to cyclic strain. Loss of paxillin or talin impaired focal adhesion formation and only affected mechanosensitivity in the absence but not presence of intercellular junctions. Further analysis revealed the adherens junction protein α-catenin as a main mechanosensor, with greatest sensitivity conferred on binding to vinculin. Our data reveal a mechanosensitive transition from cell-matrix to cell-cell adhesions on formation of keratinocyte monolayers with vinculin and α-catenin as vital players.

PMID:
30044710
PMCID:
PMC6249805
DOI:
10.1091/mbc.E17-06-0387
[Indexed for MEDLINE]
Free PMC Article

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