Haage, Amanda, Goodwin, Katharine 
ORCID: 0000-0002-4823-7491, Whitewood, Austin ORCID: 0000-0002-8255-8248, Camp, Darius, Bogutz, Aaron, Turner, Christopher T ORCID: 0000-0001-7409-4386, Granville, David J ORCID: 0000-0001-6985-2816, Lefebvre, Louis ORCID: 0000-0001-5664-9480, Plotnikov, Sergey ORCID: 0000-0002-5561-8890, Goult, Benjamin T ORCID: 0000-0002-3438-2807 et al (show 1 more authors)
(2018)
Talin Autoinhibition Regulates Cell-ECM Adhesion Dynamics and Wound Healing In Vivo.
Cell reports, 25 (9).
2401-2416.e5.
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Abstract
Cells in multicellular organisms are arranged in complex three-dimensional patterns. This requires both transient and stable adhesions with the extracellular matrix (ECM). Integrin adhesion receptors bind ECM ligands outside the cell and then, by binding the protein talin inside the cell, assemble an adhesion complex connecting to the cytoskeleton. The activity of talin is controlled by several mechanisms, but these have not been well studied in vivo. By generating mice containing the activating point mutation E1770A in talin (Tln1), which disrupts autoinhibition, we show that talin autoinhibition controls cell-ECM adhesion, cell migration, and wound healing in vivo. In particular, blocking autoinhibition gives rise to more mature, stable focal adhesions that exhibit increased integrin activation. Mutant cells also show stronger attachment to ECM and decreased traction force. Overall, these results demonstrate that modulating talin function via autoinhibition is an important mechanism for regulating multiple aspects of integrin-mediated cell-ECM adhesion in vivo.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Focal Adhesions, Extracellular Matrix, Fibroblasts, Animals, Mice, Actins, Talin, Integrins, Wound Healing, Cell Adhesion, Signal Transduction, Cell Movement, Phenotype, Mutation, Embryo, Mammalian, Biomechanical Phenomena |
| 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: | 13 Mar 2024 09:56 |
| Last Modified: | 13 Mar 2024 09:56 |
| DOI: | 10.1016/j.celrep.2018.10.098 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3179317 |
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