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J Cell Sci. 2017 May 1;130(9):1612-1624. doi: 10.1242/jcs.195362. Epub 2017 Mar 16.

Distinct focal adhesion protein modules control different aspects of mechanotransduction.

Author information

1
Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, England, UK.
2
Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, England, UK christoph.ballestrem@manchester.ac.uk.

Abstract

Focal adhesions (FAs) are macromolecular complexes that regulate cell adhesion and mechanotransduction. By performing fluorescence recovery after photobleaching (FRAP) and fluorescence loss after photoactivation (FLAP) experiments, we found that the mobility of core FA proteins correlates with their function. Structural proteins such as tensin, talin and vinculin are significantly less mobile in FAs than signaling proteins such as FAK (also known as PTK2) and paxillin. The mobilities of the structural proteins are directly influenced by substrate stiffness, suggesting that they are involved in sensing the rigidity of the extracellular environment. The turnover rates of FAK and paxillin, as well as kindlin2 (also known as FERMT2), are not influenced by substrate stiffness. By using specific Src and FAK inhibitors, we reveal that force-sensing by vinculin occurs independently of FAK and paxillin phosphorylation. However, their phosphorylation is required for downstream Rac1-driven cellular processes, such as protrusion and cell migration. Overall, we show that the FA is composed of different functional modules that separately control mechanosensing and the cellular mechano-response.

KEYWORDS:

FAK; Focal adhesion; Mechanotransduction; Paxillin; Talin; Vinculin

PMID:
28302906
PMCID:
PMC5450230
DOI:
10.1242/jcs.195362
[Indexed for MEDLINE]
Free PMC Article

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