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

Matthias Rübsam, Aaron F. Mertz, Akiharu Kubo, Susanna Marg, Christian Jüngst, Gladiola Goranci-Buzhala, Astrid C. Schauss, Valerie Horsley, Eric R. Dufresne, Markus Moser, Wolfgang Ziegler, Masayuki Amagai, Sara A. Wickström, Carien M. Niessen

研究成果: Article査読

78 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号1250
ジャーナルNature communications
8
1
DOI
出版ステータスPublished - 2017 12 1

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

フィンガープリント

「E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル