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Cell Rep. 2018 Nov 27;25(9):2401-2416.e5. doi: 10.1016/j.celrep.2018.10.098.

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

Author information

1
Department of Cellular and Physiological Sciences, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
2
School of Biosciences, Giles Ln, University of Kent, Canterbury CT2 7NZ, UK.
3
Department of Medical Genetics, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
4
Department of Pathology and Laboratory Medicine, 2211 Wesbrook Mall, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
5
Department of Cell and Systems Biology, 25 Harbord Street, University of Toronto, Toronto, ON M5S 3H7, Canada.
6
Department of Cellular and Physiological Sciences, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address: tanentz@mail.ubc.ca.

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.

KEYWORDS:

ECM; actin; adhesion; cytoskeleton; integrins; migration; talin; transgenic mice; wound healing

PMID:
30485809
DOI:
10.1016/j.celrep.2018.10.098
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