Han, Sangyoon 
ORCID: 0000-0002-1384-665X, Azarova, Evgenia, Whitewood, Austin, Bachir, Alexia, Guttierrez, Edgar, Groisman, Alex, Horwitz, Alan Rick, Goult, Benjamin ORCID: 0000-0002-3438-2807, Dean, Kevin and Danuser, Gaudenz
(2019)
Talin-vinculin precomplex drives adhesion maturation by accelerated force transmission and vinculin recruitment.
[Preprint]
Abstract
Talin, vinculin, and paxillin are mechanosensitive proteins that are recruited early to integrin-based nascent adhesions (NAs). Using machine learning, traction microscopy, single-particle-tracking, and fluorescence fluctuation analysis, we find that talin, vinculin, and paxillin are recruited in near-synchrony to NAs maturing to focal adhesions. After initial recruitment of all three proteins under minimal load, vinculin accumulates in these NAs at a ~5 fold higher rate than in non-maturing NAs and with faster growth in traction. We identify a domain in talin, R8, which exposes a vinculin-binding-site (VBS) without requiring load. Stabilizing this domain via mutation lowers load-free vinculin binding to talin, impairs maturation of NAs, and reduces the rate of additional vinculin recruitment. Taken together, our data show that talin's concurrent localization with vinculin, before engagement with integrins, is essential for NA maturation, which entails traction-mediated unfolding of talin and exposure of additional VBSs triggering further vinculin binding.
| Item Type: | Preprint |
|---|---|
| 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 09:57 |
| Last Modified: | 13 Mar 2024 09:57 |
| DOI: | 10.1101/735183 |
| Open Access URL: | https://doi.org/10.1101/735183 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3179316 |
Dimensions
Dimensions
