Force-dependent allostery of the α-catenin actin-binding domain controls adherens junction dynamics and functions. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Ishiyama, Noboru; Sarpal, Ritu; Wood, Megan; Barrick, Samantha; Nishikawa, Tadateru; Hayashi, Hanako; Kobb, Anna; Flozak, Annette; Yemelyanov, Alex; Fernandez-Gonzalez, Rodrigo; Yonemura, Shigenobu; Leckband, Deborah; Gottardi, Cara; Tepass, Ulrich; Ikura, Mitsuhiko
• Is Part Of: Nature communications. Volume 9:Issue 1(2018)
• Page Start: 1
• Page End: 17
• Publication Date: 2018-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-018-07481-7
• Languages: English
• ISSNs: 2041-1723

Abstract

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. Cell-cell adhesion mediated by catenin-cadherin complexes plays a critical role in translating the mechanical forces into physiological responses. Here the authors define a mechanism of force-dependent cadherin-actin linkage dynamically regulated through the actin-binding domain of α-catenin.