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Talin Autoinhibition Regulates Cell-ECM Adhesion Dynamics and Wound Healing In Vivo

Haage, A., Goodwin, K., Whitewood, A.J., Camp, D., Bogutz, A., Turner, C.T., Granville, D.J., Lefebvre, L., Plotnikov, S., Goult, Benjamin T., and others. (2018) Talin Autoinhibition Regulates Cell-ECM Adhesion Dynamics and Wound Healing In Vivo. Cell Reports, 25 (9). pp. 2401-2416. ISSN 2211-1247. (doi:10.1016/j.celrep.2018.10.098)

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
DOI/Identification number: 10.1016/j.celrep.2018.10.098
Uncontrolled keywords: adhesion, migration, talin, integrins, ECM, wound healing, actin, cytoskeleton
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Ben Goult
Date Deposited: 30 Nov 2018 21:35 UTC
Last Modified: 28 Aug 2019 10:19 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/70530 (The current URI for this page, for reference purposes)
Goult, Benjamin T.: https://orcid.org/0000-0002-3438-2807
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