Abstract

The actin cytoskeleton mediates mechanical coupling between cells and their tissue microenvironments. The architecture and composition of actin networks are modulated by force, but it is unclear how interactions between actin filaments (F-actin) and associated proteins are mechanically regulated. Here, we employ both optical trapping and biochemical reconstitution with myosin motor proteins to show single piconewton forces applied solely to F-actin enhance binding by the human version of the essential cell-cell adhesion protein αE-catenin, but not its homolog vinculin. Cryo-electron microscopy structures of both proteins bound to F-actin reveal unique rearrangements that facilitate their flexible C-termini refolding to engage distinct interfaces. Truncating α-catenin's C-terminus eliminates force-activated F-actin binding, and addition of this motif to vinculin confers force-activated binding, demonstrating that α-catenin's C-terminus is a modular detector of F-actin tension. Our studies establish that piconewton force on F-actin can enhance partner binding, which we propose mechanically regulates cellular adhesion through a-catenin.

Data availability

The atomic coordinates for the metavinculin ABD-F-actin complex and α-catenin ABD-F-actin complex have been deposited in the Protein Data Bank (PDB) with accession codes 6UPW and 6UPV, and the corresponding cryo-EM density maps in the Electron Microscopy Data Bank (EMDB) with accession codes EMD-20844 and EMD-20843.The code for analyzing TIRF movies is freely available as an ImageJ plugin with a graphical user interface at https://github.com/alushinlab/ActinEnrichment. All other data are available in the manuscript or supplementary materials.

The following data sets were generated

Article and author information

Author details

  1. Lin Mei

    Laboratory of Structural Biophysics and Mechanobiology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5056-4547
  2. Santiago Espinosa de los Reyes

    Laboratory of Structural Biophysics and Mechanobiology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4510-8296
  3. Matthew J Reynolds

    Laboratory of Structural Biophysics and Mechanobiology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2501-9280
  4. Rachel Leicher

    Laboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Shixin Liu

    Laboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4238-7066
  6. Gregory M Alushin

    Laboratory of Structural Biophysics and Mechanobiology, The Rockefeller University, New York, United States
    For correspondence
    galushin@rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7250-4484

Funding

Irma T. Hirschl Trust (Research Award)

  • Gregory M Alushin

Pew Charitable Trusts (Pew Scholar Award)

  • Gregory M Alushin

National Institutes of Health (5DP5OD017885)

  • Gregory M Alushin

National Institutes of Health (1DP2HG010510)

  • Shixin Liu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Andrew P Carter, MRC Laboratory of Molecular Biology, United Kingdom

Version history

  1. Received: August 27, 2020
  2. Accepted: September 21, 2020
  3. Accepted Manuscript published: September 24, 2020 (version 1)
  4. Version of Record published: October 26, 2020 (version 2)

Copyright

© 2020, Mei 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. Lin Mei
  2. Santiago Espinosa de los Reyes
  3. Matthew J Reynolds
  4. Rachel Leicher
  5. Shixin Liu
  6. Gregory M Alushin
(2020)
Molecular mechanism for direct actin force-sensing by α-catenin
eLife 9:e62514.
https://doi.org/10.7554/eLife.62514

Share this article

https://doi.org/10.7554/eLife.62514

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