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.

Details

Title
Force-dependent allostery of the α-catenin actin-binding domain controls adherens junction dynamics and functions
Author
Ishiyama, Noboru 1   VIAFID ORCID Logo  ; Sarpal, Ritu 2 ; Wood, Megan N 3 ; Barrick, Samantha K 4 ; Nishikawa, Tadateru 1 ; Hayashi, Hanako 5 ; Kobb, Anna B 6 ; Flozak, Annette S 3 ; Yemelyanov, Alex 3 ; Fernandez-Gonzalez, Rodrigo 7   VIAFID ORCID Logo  ; Yonemura, Shigenobu 8 ; Leckband, Deborah E 9 ; Gottardi, Cara J 10   VIAFID ORCID Logo  ; Tepass, Ulrich 2 ; Ikura, Mitsuhiko 11 

1  Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada 
2  Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada 
3  Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA 
4  Department of Chemistry, University of Illinois, Urbana, IL, USA 
5  RIKEN Center for Life Science Technologies, Kobe, Hyogo, Japan 
6  Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada 
7  Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada 
8  RIKEN Center for Life Science Technologies, Kobe, Hyogo, Japan; Department of Cell Biology, Tokushima University Graduate School of Medical Science, Tokushima, Japan 
9  Department of Chemistry, University of Illinois, Urbana, IL, USA; Department of Chemical and Biomolecular Engineering, University of Illinois, Urbana, IL, USA 
10  Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Department of Cellular and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA 
11  Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada 
Pages
1-17
Publication year
2018
Publication date
Nov 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-07481-7
ProQuest document ID
2139590188
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.