Mechanism of the cadherin-catenin F-actin catch bond interaction

  1. Amy Wang
  2. Alexander R Dunn  Is a corresponding author
  3. William I Weis  Is a corresponding author
  1. Stanford University, United States

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

  1. Amy Wang

    Department of Chemical Engineering, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4139-4563
  2. Alexander R Dunn

    Department of Chemical Engineering, Stanford University, Stanford, United States
    For correspondence
    alex.dunn@stanford.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6096-4600
  3. William I Weis

    Department of Structural Biology, Stanford University, Stanford, United States
    For correspondence
    bill.weis@stanford.edu
    Competing interests
    William I Weis, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5583-6150

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

  1. Christopher P Hill, University of Utah School of Medicine, United States

Publication history

  1. Received: May 12, 2022
  2. Accepted: August 1, 2022
  3. Accepted Manuscript published: August 1, 2022 (version 1)
  4. Accepted Manuscript updated: August 2, 2022 (version 2)

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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  1. Amy Wang
  2. Alexander R Dunn
  3. William I Weis
(2022)
Mechanism of the cadherin-catenin F-actin catch bond interaction
eLife 11:e80130.
https://doi.org/10.7554/eLife.80130

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