Force-dependent allostery of the α-catenin actinbinding domain controls adherens junction dynamics and functions

• Ishiyama, Noboru

• Sarpal, Ritu

• Wood, Megan N.

• Barrick, Samantha K.

• Nishikawa, Tadateru

• Hayashi, Hanako

• Kobb, Anna B.

• Flozak, Annette S.

• Yemelyanov, Alex

• Fernandez-Gonzalez, Rodrigo

• Yonemura, Shigenobu

• Leckband, Deborah E.

• Gottardi, Cara J.

• Tepass, Ulrich

• Ikura, Mitsuhiko

Abstract

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.

Journal

• Nature Communications

  Nature Communications 9 5121-, 2018-11-30

  Springer Nature

Details

• CRID: 1050006144190340224
• NII Article ID: 120006952375
• NII Book ID: AA12645905
• ISSN: 20411723
• DOI: 10.1038/s41467-018-07481-7
• Web Site: http://repo.lib.tokushima-u.ac.jp/114825
• Web Site: https://www.nature.com/articles/s41467-018-07481-7.pdf
• Web Site: https://www.nature.com/articles/s41467-018-07481-7
• Text Lang: en
• Article Type: journal article
• Data Source:
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