TY - JOUR
T1 - E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning
AU - Rübsam, Matthias
AU - Mertz, Aaron F.
AU - Kubo, Akiharu
AU - Marg, Susanna
AU - Jüngst, Christian
AU - Goranci-Buzhala, Gladiola
AU - Schauss, Astrid C.
AU - Horsley, Valerie
AU - Dufresne, Eric R.
AU - Moser, Markus
AU - Ziegler, Wolfgang
AU - Amagai, Masayuki
AU - Wickström, Sara A.
AU - Niessen, Carien M.
N1 - Funding Information:
We would like to thank Christian Michels for help with barrier assays, members of the Niessen lab, Sandra Iden, and Hisham Bazzi (University of Cologne) and especially Kathleen J. Green (Northwestern University), Rudolf Merkel, and Bernd Hoffmann (Julich Research Center) for discussion and critical input. We also thank Akira Nagafuchi for the generous gift of the α18 AB and Franscesca Mascia and Stuart Yuspa (NIH) for providing us with tissue sections of epidermal EGFR knockout mice. Furthermore we greatly acknowledge Sabine Eming (University of Cologne) for providing human skin samples. We greatly acknowledge the funding by DFG: SFB 829 A1, Z2, and SPP 1782 grant no. NI1234/6-1.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41467-017-01170-7
DO - 10.1038/s41467-017-01170-7
M3 - Article
C2 - 29093447
AN - SCOPUS:85032670876
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1250
ER -