Talin Autoinhibition Regulates Cell-ECM Adhesion Dynamics and Wound Healing In Vivo
| Autor: | Benjamin T. Goult, Aaron B. Bogutz, Katharine Goodwin, Louis Lefebvre, Guy Tanentzapf, Austin J. Whitewood, David J. Granville, Darius Camp, Christopher T. Turner, Sergey V. Plotnikov, Amanda Haage |
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| Přispěvatelé: | Haage, Amanda, Goodwin, Katharine, Whitewood, Austin, Camp, Darius, Bogutz, Aaron, Turner, Christopher T, Granville, David J, Lefebvre, Louis, Plotnikov, Sergey, Goult, Benjamin T, Tanentzapf, Guy |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Talin Integrins Integrin wound healing macromolecular substances transgenic mice migration General Biochemistry Genetics and Molecular Biology Extracellular matrix Focal adhesion 03 medical and health sciences Mice QH301 0302 clinical medicine Cell Movement Cell Adhesion Animals Cytoskeleton Actin Focal Adhesions Wound Healing ECM biology Chemistry talin Cell migration cytoskeleton Adhesion Fibroblasts Embryo Mammalian Actins Cell biology Biomechanical Phenomena Extracellular Matrix adhesion 030104 developmental biology Phenotype TLN1 Mutation biology.protein integrins actin 030217 neurology & neurosurgery Signal Transduction |
| ISSN: | 2211-1247 |
| Popis: | usc 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. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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