Universität zu Köln

Ruebsam, Matthias, Mertz, Aaron F., Kubo, Akiharu, Marg, Susanna, Juengst, Christian, Goranci-Buzhala, Gladiola, Schauss, Astrid C., Horsley, Valerie, Dufresne, Eric R., Moser, Markus, Ziegler, Wolfgang, Amagai, Masayuki ORCID: 0000-0003-3314-7052, Wickstroem, Sara A. and Niessen, Carien M. (2017). E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning. Nat. Commun., 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ruebsam, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Mertz, Aaron F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kubo, Akiharu UNSPECIFIED UNSPECIFIED UNSPECIFIED Marg, Susanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Juengst, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Goranci-Buzhala, Gladiola UNSPECIFIED UNSPECIFIED UNSPECIFIED Schauss, Astrid C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Horsley, Valerie UNSPECIFIED UNSPECIFIED UNSPECIFIED Dufresne, Eric R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Moser, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Ziegler, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Amagai, Masayuki UNSPECIFIED orcid.org/0000-0003-3314-7052 UNSPECIFIED Wickstroem, Sara A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Niessen, Carien M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-212962
DOI:	10.1038/s41467-017-01170-7
Journal or Publication Title:	Nat. Commun.
Volume:	8
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL-ADHESION MOLECULE; ALPHA-CATENIN; F-ACTIN; EPIDERMAL BARRIER; VE-CADHERIN; FORCE; RECEPTOR; COMPLEX; MICE; MECHANISMS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21296