Molecular mechanism for direct actin force-sensing by α-catenin
The actin cytoskeleton mediates mechanical coupling between cells and their tissue microenvironments. The architecture and composition of actin networks are modulated by force; however, it is unclear how interactions between actin filaments (F-actin) and associated proteins are mechanically regulate...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/62514 |
| _version_ | 1811180311743037440 |
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| author | Lin Mei Santiago Espinosa de los Reyes Matthew J Reynolds Rachel Leicher Shixin Liu Gregory M Alushin |
| author_facet | Lin Mei Santiago Espinosa de los Reyes Matthew J Reynolds Rachel Leicher Shixin Liu Gregory M Alushin |
| author_sort | Lin Mei |
| collection | DOAJ |
| description | The actin cytoskeleton mediates mechanical coupling between cells and their tissue microenvironments. The architecture and composition of actin networks are modulated by force; however, 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 α-catenin. |
| first_indexed | 2024-04-11T09:00:44Z |
| format | Article |
| id | doaj.art-b10232867b744f808e382a22565469d5 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:00:44Z |
| publishDate | 2020-09-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-b10232867b744f808e382a22565469d52022-12-22T04:32:48ZengeLife Sciences Publications LtdeLife2050-084X2020-09-01910.7554/eLife.62514Molecular mechanism for direct actin force-sensing by α-cateninLin Mei0https://orcid.org/0000-0002-5056-4547Santiago Espinosa de los Reyes1https://orcid.org/0000-0003-4510-8296Matthew J Reynolds2https://orcid.org/0000-0002-2501-9280Rachel Leicher3Shixin Liu4https://orcid.org/0000-0003-4238-7066Gregory M Alushin5https://orcid.org/0000-0001-7250-4484Laboratory of Structural Biophysics and Mechanobiology, The Rockefeller University, New York, United States; Tri-Institutional PhD Program in Chemical Biology, The Rockefeller University, New York, United StatesLaboratory of Structural Biophysics and Mechanobiology, The Rockefeller University, New York, United StatesLaboratory of Structural Biophysics and Mechanobiology, The Rockefeller University, New York, United StatesTri-Institutional PhD Program in Chemical Biology, The Rockefeller University, New York, United States; Laboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, United StatesLaboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, United StatesLaboratory of Structural Biophysics and Mechanobiology, The Rockefeller University, New York, United StatesThe actin cytoskeleton mediates mechanical coupling between cells and their tissue microenvironments. The architecture and composition of actin networks are modulated by force; however, 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 α-catenin.https://elifesciences.org/articles/62514cryo-electron microscopyactin cytoskeletonmechanobiologymechanosensationcell adhesionsingle molecule biophysics |
| spellingShingle | Lin Mei Santiago Espinosa de los Reyes Matthew J Reynolds Rachel Leicher Shixin Liu Gregory M Alushin Molecular mechanism for direct actin force-sensing by α-catenin eLife cryo-electron microscopy actin cytoskeleton mechanobiology mechanosensation cell adhesion single molecule biophysics |
| title | Molecular mechanism for direct actin force-sensing by α-catenin |
| title_full | Molecular mechanism for direct actin force-sensing by α-catenin |
| title_fullStr | Molecular mechanism for direct actin force-sensing by α-catenin |
| title_full_unstemmed | Molecular mechanism for direct actin force-sensing by α-catenin |
| title_short | Molecular mechanism for direct actin force-sensing by α-catenin |
| title_sort | molecular mechanism for direct actin force sensing by α catenin |
| topic | cryo-electron microscopy actin cytoskeleton mechanobiology mechanosensation cell adhesion single molecule biophysics |
| url | https://elifesciences.org/articles/62514 |
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