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ID 114825
著者
Ishiyama, Noboru University Health Network
Sarpal, Ritu University of Toronto
Wood, Megan N. Northwestern University
Barrick, Samantha K. University of Illinois
Nishikawa, Tadateru University Health Network
Hayashi, Hanako RIKEN
Kobb, Anna B. University of Toronto
Flozak, Annette S. Northwestern University
Yemelyanov, Alex Northwestern University
Fernandez-Gonzalez, Rodrigo University of Toronto
Leckband, Deborah E. University of Illinois
Gottardi, Cara J. Northwestern University
Tepass, Ulrich University of Toronto
Ikura, Mitsuhiko University Health Network|University of Toronto
資料タイプ
学術雑誌論文
抄録
α-catenin is a key mechanosensor that forms force-dependent interactions with F-actin, thereby coupling the cadherin-catenin complex to the actin cytoskeleton at adherens junctions (AJs). However, the molecular mechanisms by which α-catenin engages F-actin under tension remained elusive. Here we show that the α1-helix of the α-catenin actin-binding domain (αcat-ABD) is a mechanosensing motif that regulates tension-dependent F-actin binding and bundling. αcat-ABD containing an α1-helix-unfolding mutation (H1) shows enhanced binding to F-actin in vitro. Although full-length α-catenin-H1 can generate epithelial monolayers that resist mechanical disruption, it fails to support normal AJ regulation in vivo. Structural and simulation analyses suggest that α1-helix allosterically controls the actin-binding residue V796 dynamics. Crystal structures of αcat-ABD-H1 homodimer suggest that α-catenin can facilitate actin bundling while it remains bound to E-cadherin. We propose that force-dependent allosteric regulation of αcat-ABD promotes dynamic interactions with F-actin involved in actin bundling, cadherin clustering, and AJ remodeling during tissue morphogenesis.
掲載誌名
Nature Communications
ISSN
20411723
cat書誌ID
AA12645905
出版者
Springer Nature
9
開始ページ
5121
発行日
2018-11-30
権利情報
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
© The Author(s) 2018
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言語
eng
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出版社版
部局
医学系