Mechanism of the cadherin-catenin F-actin catch bond interaction
Abstract
Mechanotransduction at cell-cell adhesions is crucial for the structural integrity, organization, and morphogenesis of epithelia. At cell-cell junctions, ternary E-cadherin/β-catenin/αE-catenin complexes sense and transmit mechanical load by binding to F-actin. The interaction with F-actin, described as a two-state catch bond, is weak in solution but is strengthened by applied force due to force-dependent transitions between weak and strong actin-binding states. Here, we provide direct evidence from optical trapping experiments that the catch bond property principally resides in the αE-catenin actin-binding domain (ABD). Consistent with our previously proposed model, deletion of the first helix of the five-helix ABD bundle enables stable interactions with F-actin under minimal load that are well-described by a single-state slip bond, even when αE-catenin is complexed with β-catenin and E-cadherin. Our data argue for a conserved catch bond mechanism for adhesion proteins with structurally similar ABDs. We also demonstrate that a stably bound ABD strengthens load-dependent binding interactions between a neighboring complex and F-actin, but the presence of the other αE-catenin domains weakens this effect. These results provide mechanistic insight to the cooperative binding of the cadherin-catenin complex to F-actin, which regulate dynamic cytoskeletal linkages in epithelial tissues.
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Author details
Funding
National Institutes of Health (R01GM114462)
- Alexander R Dunn
- William I Weis
National Institutes of Health (R35GM130332)
- Alexander R Dunn
National Institutes of Health (R35GM131747)
- William I Weis
National Science Foundation (Graduate Fellowship)
- Amy Wang
Stanford University (Stanford Graduate Fellowship)
- Amy Wang
National Institutes of Health (T32GM120007)
- Amy Wang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Christopher P Hill, University of Utah School of Medicine, United States
Version history
- Preprint posted: May 6, 2022 (view preprint)
- Received: May 12, 2022
- Accepted: August 1, 2022
- Accepted Manuscript published: August 1, 2022 (version 1)
- Accepted Manuscript updated: August 2, 2022 (version 2)
- Version of Record published: August 24, 2022 (version 3)
Copyright
© 2022, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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