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Nat Commun. 2015 Dec 4;6:10038. doi: 10.1038/ncomms10038.

Vinculin controls talin engagement with the actomyosin machinery.

Author information

1
Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, UK.
2
Department of Microbiology, Complutense, University of Madrid, 28040 Madrid, Spain.
3
Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
4
Vanderbilt Centre for Kidney Disease, Vanderbilt Division of Nephrology, S-3223 Medical Centre, North Nashville, Tennessee, USA.
5
Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
6
School of Biosciences, University of Kent, Canterbury, KENT CT2 7NJ, UK.

Abstract

The link between extracellular-matrix-bound integrins and intracellular F-actin is essential for cell spreading and migration. Here, we demonstrate how the actin-binding proteins talin and vinculin cooperate to provide this link. By expressing structure-based talin mutants in talin null cells, we show that while the C-terminal actin-binding site (ABS3) in talin is required for adhesion complex assembly, the central ABS2 is essential for focal adhesion (FA) maturation. Thus, although ABS2 mutants support cell spreading, the cells lack FAs, fail to polarize and exert reduced force on the surrounding matrix. ABS2 is inhibited by the preceding mechanosensitive vinculin-binding R3 domain, and deletion of R2R3 or expression of constitutively active vinculin generates stable force-independent FAs, although cell polarity is compromised. Our data suggest a model whereby force acting on integrin-talin complexes via ABS3 promotes R3 unfolding and vinculin binding, activating ABS2 and locking talin into an actin-binding configuration that stabilizes FAs.

PMID:
26634421
PMCID:
PMC4686655
DOI:
10.1038/ncomms10038
[Indexed for MEDLINE]
Free PMC Article

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