Atherton, Paul, Lausecker, Franziska, Carisey, Alexandre, Gilmore, Andrew, Critchley, David, Barsukov, Igor 
ORCID: 0000-0003-4406-9803 and Ballestrem, Christoph
(2020)
Relief of talin autoinhibition triggers a force-independent association with vinculin.
JOURNAL OF CELL BIOLOGY, 219 (1).
e201903134-.
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Relief of talin autoinhibition triggers a force-independent association with vinculin.pdf - Published version Download (6MB) | Preview |
Abstract
Talin, vinculin, and paxillin are core components of the dynamic link between integrins and actomyosin. Here, we study the mechanisms that mediate their activation and association using a mitochondrial-targeting assay, structure-based mutants, and advanced microscopy. As expected, full-length vinculin and talin are autoinhibited and do not interact with each other. However, contrary to previous models that propose a critical role for forces driving talin-vinculin association, our data show that force-independent relief of autoinhibition is sufficient to mediate their tight interaction. We also found that paxillin can bind to both talin and vinculin when either is inactive. Further experiments demonstrated that adhesions containing paxillin and vinculin can form without talin following integrin activation. However, these are largely deficient in exerting traction forces to the matrix. Our observations lead to a model whereby paxillin contributes to talin and vinculin recruitment into nascent adhesions. Activation of the talin-vinculin axis subsequently leads to the engagement with the traction force machinery and focal adhesion maturation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Cells, Cultured, Focal Adhesions, Fibroblasts, Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Talin, Vinculin, Protein Binding, Stress, Mechanical, Paxillin, Actin Cytoskeleton |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 30 Jun 2021 10:52 |
| Last Modified: | 18 Jan 2023 21:37 |
| DOI: | 10.1083/jcb.201903134 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3128249 |
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