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

Ruebsam, M., Mertz, A. F., Kubo, A., Marg, S., Juengst, C., Goranci-Buzhala, G., et al. (2017). E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning. Nature Communications, 8: 1250. doi:10.1038/s41467-017-01170-7.

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s41467-017-01170-7.pdf (Publisher version), 13MB
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Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License.

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 Creators:
Ruebsam, Matthias1, Author
Mertz, Aaron F.1, Author
Kubo, Akiharu1, Author
Marg, Susanna1, Author
Juengst, Christian1, Author
Goranci-Buzhala, Gladiola1, Author
Schauss, Astrid C.1, Author
Horsley, Valerie1, Author
Dufresne, Eric R.1, Author
Moser, Markus2, Author              
Ziegler, Wolfgang1, Author
Amagai, Masayuki1, Author
Wickstroem, Sara A.1, Author
Niessen, Carien M.1, Author
Affiliations:
1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Free keywords: CELL-ADHESION MOLECULE; ALPHA-CATENIN; F-ACTIN; EPIDERMAL BARRIER; VE-CADHERIN; FORCE; RECEPTOR; COMPLEX; MICE; MECHANISMSScience & Technology - Other Topics;
 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.

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Language(s): eng - English
 Dates: 2017
 Publication Status: Published online
 Pages: 16
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 8 Sequence Number: 1250 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723