Talin-activated vinculin interacts with branched actin networks to initiate bundles

Abstract
Data availability
Article and author information
Metrics

Abstract

Vinculin plays a fundamental role in integrin-mediated cell adhesion. Activated by talin, it interacts with diverse adhesome components, enabling mechanical coupling between the actin cytoskeleton and the extracellular matrix. Here we studied the interactions of activated full-length vinculin with actin and the way it regulates the organization and dynamics of the Arp2/3 complex-mediated branched actin network. Through a combination of surface patterning and light microscopy experiments we show that vinculin can bundle dendritic actin networks through rapid binding and filament crosslinking. We show that vinculin promotes stable but flexible actin bundles having a mixed-polarity organization, as confirmed cryo-electron tomography. Adhesion-like synthetic design of vinculin activation by surface-bound talin revealed that clustered vinculin can initiate and immobilize bundles from mobile Arp2/3-branched networks. Our results provide a molecular basis for coordinate actin bundle formation at nascent adhesions.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. The structural data is deposited to the EMD , access number EMD-10737, and two tomographic volumes were deposited in EMPIAR under the accession number EMPIAR-10548.

The following data sets were generated

(2020) Actin filament structure from vinculin-induced bundles
EMDB, EMD-10737.

https://https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-10737
(2020) Talin-activated vinculin interacts with branched actin networks to initiate bundles
EMPIAR , EMPIAR-10548.

https://www.ebi.ac.uk/pdbe/emdb/empiar/entry/10548/

The following previously published data sets were used

1. Galkin VE
2. Orlova A
3. Vos MR
4. Schroder GF
5. Egelman EH
(2015) Near-Atomic Resolution for One State of F-Actin
EMDB, EMD-6179.

https://www.ebi.ac.uk/pdbe/entry/pdb/3j8i

Article and author information

Author details

Rajaa Boujemaa-Paterski

Department of Biochemistry, University of Zurich, Zurich, Switzerland

For correspondence
r.boujemaa@bioc.uzh.ch

Competing interests
The authors declare that no competing interests exist.
Bruno Martins

Biochemistry, University of Zürich, Zurich, Switzerland

Competing interests
The authors declare that no competing interests exist.
Matthias Eibauer

Biochemistry, University of Zürich, Zurich, Switzerland

Competing interests
The authors declare that no competing interests exist.
Charlie T Beals

Biochemistry, University of Zürich, Zurich, Switzerland

Competing interests
The authors declare that no competing interests exist.
Benjamin Geiger

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel

Competing interests
The authors declare that no competing interests exist.
Ohad Medalia

Biochemistry, University of Zürich, Zurich, Switzerland

For correspondence
omedalia@bioc.uzh.ch

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0994-2937

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_179418)

Ohad Medalia

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.