Vinculin controls talin engagement with the actomyosin machinery.



Atherton, Paul, Stutchbury, Ben, Wang, De-Yao, Jethwa, Devina, Tsang, Ricky, Meiler-Rodriguez, Eugenia, Wang, Pengbo, Bate, Neil, Zent, Roy, Barsukov, Igor L ORCID: 0000-0003-4406-9803
et al (show 3 more authors) (2015) Vinculin controls talin engagement with the actomyosin machinery. Nature communications, 6 (1). 10038-.

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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.

Item Type: Article
Uncontrolled Keywords: cell migration, cell polarity, cell signalling
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 13 Mar 2024 09:54
Last Modified: 13 Mar 2024 09:54
DOI: 10.1038/ncomms10038
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3179323