Talin1 is critical for force-dependent reinforcement of initial integrin-cytoskeleton bonds but not tyrosine kinase activation

Grégory Giannone, Guoying Jiang, Deborah H. Sutton, David R. Critchley, Michael Sheetz

Research output: Contribution to journalArticle

200 Citations (Scopus)

Abstract

Cells rapidly transduce forces exerted on extracellular matrix contacts into tyrosine kinase activation and recruitment of cytoskeletal proteins to reinforce integrin-cytoskeleton connections and initiate adhesion site formation. The relationship between these two processes has not been defined, particularly at the submicrometer level. Using talin1-deficient cells, it appears that talin1 is critical for building early mechanical linkages. Deletion of talin1 blocked laser tweezers, force-dependent reinforcement of submicrometer fibronectin-coated beads and early formation of adhesion sites in response to force, even though Src family kinases, focal adhesion kinase, and spreading were activated normally. Recruitment of vinculin and paxillin to sites of force application also required talin1. FilaminA had a secondary role in strengthening fibronectin-integrin-cytoskeleton connections and no role in stretch-dependent adhesion site assembly. Thus, force-dependent activation of tyrosine kinases is independent of early force-dependent structural changes that require talin1 as part of a critical scaffold.

Original languageEnglish (US)
Pages (from-to)409-419
Number of pages11
JournalJournal of Cell Biology
Volume163
Issue number2
DOIs
StatePublished - Oct 27 2003
Externally publishedYes

Fingerprint

Cytoskeleton
Fibronectins
Integrins
Protein-Tyrosine Kinases
Optical Tweezers
Paxillin
Vinculin
Focal Adhesion Protein-Tyrosine Kinases
Cytoskeletal Proteins
src-Family Kinases
Extracellular Matrix

Keywords

  • Actin cytoskeleton
  • Integrin
  • Mechano-sensing
  • Talin
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Talin1 is critical for force-dependent reinforcement of initial integrin-cytoskeleton bonds but not tyrosine kinase activation. / Giannone, Grégory; Jiang, Guoying; Sutton, Deborah H.; Critchley, David R.; Sheetz, Michael.

In: Journal of Cell Biology, Vol. 163, No. 2, 27.10.2003, p. 409-419.

Research output: Contribution to journalArticle

Giannone, Grégory ; Jiang, Guoying ; Sutton, Deborah H. ; Critchley, David R. ; Sheetz, Michael. / Talin1 is critical for force-dependent reinforcement of initial integrin-cytoskeleton bonds but not tyrosine kinase activation. In: Journal of Cell Biology. 2003 ; Vol. 163, No. 2. pp. 409-419.
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AU - Sheetz, Michael

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