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Talin Autoinhibition Regulates Cell-ECM Adhesion Dynamics and Wound Healing In Vivo.
- Source :
-
Cell reports [Cell Rep] 2018 Nov 27; Vol. 25 (9), pp. 2401-2416.e5. - Publication Year :
- 2018
-
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.<br /> (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Actins metabolism
Animals
Biomechanical Phenomena
Cell Adhesion
Cell Movement
Embryo, Mammalian metabolism
Fibroblasts metabolism
Focal Adhesions metabolism
Integrins metabolism
Mice
Mutation genetics
Phenotype
Signal Transduction
Talin genetics
Extracellular Matrix metabolism
Talin metabolism
Wound Healing
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 25
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 30485809
- Full Text :
- https://doi.org/10.1016/j.celrep.2018.10.098