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Vinculin controls talin engagement with the actomyosin machinery

Atherton, Paul, Stuchbury, Ben, Wang, De-Yao, Jethwa, Devina, Tsang, Ricky, Meiler-Rodriguez, Eugenia, Wang, Pengbo, Bate, Neil, Zent, Roy, Barsukov, Igor L, and others. (2015) Vinculin controls talin engagement with the actomyosin machinery. Nature Communications, 6 . pp. 1-12. ISSN 2041-1723. (doi:10.1038/ncomms10038) (KAR id:52694)

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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.

Item Type: Article
DOI/Identification number: 10.1038/ncomms10038
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
Depositing User: Ben Goult
Date Deposited: 04 Dec 2015 14:21 UTC
Last Modified: 06 Feb 2020 10:20 UTC
Resource URI: (The current URI for this page, for reference purposes)
Goult, Benjamin T:
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