Molecular mechanism for direct actin force-sensing by α-catenin
- The Rockefeller University, United States
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.
Article and author information
Author details
Santiago Espinosa de los Reyes
Matthew J Reynolds
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.
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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Molecular mechanism for direct actin force-sensing by α-catenin
eLife 9:e62514.
https://doi.org/10.7554/eLife.62514
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