Relief of talin autoinhibition triggers a force-independent association with vinculin.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
06 01 2020
06 01 2020
Historique:
received:
25
03
2019
revised:
12
09
2019
accepted:
21
10
2019
entrez:
10
12
2019
pubmed:
10
12
2019
medline:
28
7
2020
Statut:
ppublish
Résumé
Talin, vinculin, and paxillin are core components of the dynamic link between integrins and actomyosin. Here, we study the mechanisms that mediate their activation and association using a mitochondrial-targeting assay, structure-based mutants, and advanced microscopy. As expected, full-length vinculin and talin are autoinhibited and do not interact with each other. However, contrary to previous models that propose a critical role for forces driving talin-vinculin association, our data show that force-independent relief of autoinhibition is sufficient to mediate their tight interaction. We also found that paxillin can bind to both talin and vinculin when either is inactive. Further experiments demonstrated that adhesions containing paxillin and vinculin can form without talin following integrin activation. However, these are largely deficient in exerting traction forces to the matrix. Our observations lead to a model whereby paxillin contributes to talin and vinculin recruitment into nascent adhesions. Activation of the talin-vinculin axis subsequently leads to the engagement with the traction force machinery and focal adhesion maturation.
Identifiants
pubmed: 31816055
pii: 132632
doi: 10.1083/jcb.201903134
pmc: PMC7039207
pii:
doi:
Substances chimiques
Paxillin
0
Pxn protein, mouse
0
Talin
0
Vcl protein, mouse
0
Tln1 protein, mouse
0
Vinculin
125361-02-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/P000681/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M01150X/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203128/Z/16/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202860/Z/16/Z
Pays : United Kingdom
Informations de copyright
© 2019 Atherton et al.
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