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Nat Commun. 2017 Nov 1;8(1):1250. doi: 10.1038/s41467-017-01170-7.

E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning.

Author information

1
Department of Dermatology, University of Cologne, Cologne, 50931, Germany.
2
Cologne Excellence Cluster for Stress Responses in Ageing-associated diseases (CECAD), Cologne, 50931, Germany.
3
Center for Molecular Medicine Cologne (CMMC) University of Cologne, Cologne, 50931, Germany.
4
Department of Physics, Yale University, New Haven, CT, 06520, USA.
5
Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY, 10065, USA.
6
Department of Dermatology, Keio University School of Medicine, Tokyo, 160-8582, Japan.
7
Hannover Medical School, 30625, Hannover, Germany.
8
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, 06520, USA.
9
Departments of Mechanical Engineering and Materials Science, Chemical and Environmental Engineering, and Cell Biology, Yale University, New Haven, CT, 06520, USA.
10
Max Planck Institute for Biochemistry, Am Klopferspitz 18, Martinsried, 82152, Germany.
11
Paul Gerson Unna Group 'Skin Homeostasis and Ageing', Max Planck Institute for Biology of Ageing, Cologne, 50931, Germany.
12
Department of Dermatology, University of Cologne, Cologne, 50931, Germany. carien.niessen@uni-koeln.de.
13
Cologne Excellence Cluster for Stress Responses in Ageing-associated diseases (CECAD), Cologne, 50931, Germany. carien.niessen@uni-koeln.de.
14
Center for Molecular Medicine Cologne (CMMC) University of Cologne, Cologne, 50931, Germany. carien.niessen@uni-koeln.de.

Abstract

Generation of a barrier in multi-layered epithelia like the epidermis requires restricted positioning of functional tight junctions (TJ) to the most suprabasal viable layer. This positioning necessitates tissue-level polarization of junctions and the cytoskeleton through unknown mechanisms. Using quantitative whole-mount imaging, genetic ablation, and traction force microscopy and atomic force microscopy, we find that ubiquitously localized E-cadherin coordinates tissue polarization of tension-bearing adherens junction (AJ) and F-actin organization to allow formation of an apical TJ network only in the uppermost viable layer. Molecularly, E-cadherin localizes and tunes EGFR activity and junctional tension to inhibit premature TJ complex formation in lower layers while promoting increased tension and TJ stability in the granular layer 2. In conclusion, our data identify an E-cadherin-dependent mechanical circuit that integrates adhesion, contractile forces and biochemical signaling to drive the polarized organization of junctional tension necessary to build an in vivo epithelial barrier.

PMID:
29093447
PMCID:
PMC5665913
DOI:
10.1038/s41467-017-01170-7
[Indexed for MEDLINE]
Free PMC Article

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