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ID 114825
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
Content Type
Journal Article
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.
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Nature Communications
Springer Nature
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© The Author(s) 2018
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Medical Sciences