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BUNDLEFORCE SIGNED

Unravelling the Mechanosensitivity of Actin Bundles in Filopodia

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EC-Contrib. €

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Project "BUNDLEFORCE" data sheet

The following table provides information about the project.

Coordinator
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS 

Organization address
address: RUE MICHEL ANGE 3
city: PARIS
postcode: 75794
website: www.cnrs.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country France [FR]
 Total cost 1˙499˙190 €
 EC max contribution 1˙499˙190 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-03-01   to  2021-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS FR (PARIS) coordinator 1˙499˙190.00

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 Project objective

Eukaryotic cells constantly convert signals between biochemical energy and mechanical work to timely accomplish many key functions such as migration, division or development. Filopodia are essential finger-like structures that emerge at the cell front to orient the cell in response to its chemical and mechanical environment. Yet, the molecular interactions that make the filopodia mechanosensitive are not known. To tackle this challenge we propose unique biophysical in vitro and in vivo experiments of increasing complexity. Here we will focus on how the underlying actin filament bundle regulates filopodium growth and retraction cycles at the micrometer and seconds scales. These parallel actin filaments are mainly elongated at their barbed-end by formins and cross-linked by bundling proteins such as fascins. We aim to: 1) Elucidate how formin and fascin functions are regulated by mechanics at the single filament level. We will investigate how formin partners and competitors present in filopodia affect formin processivity; how fascin affinity for the side of filaments is modified by filament tension and formin presence at the barbed-end. 2) Reconstitute filopodium-like actin bundles in vitro to understand how actin bundle size and fate are regulated down to the molecular scale. Using a unique experimental setup that combines microfluidics and optical tweezers, we will uncover for the first time actin bundles mechanosensitive capabilities, both in tension and compression. 3) Decipher in vivo the mechanics of actin bundles in filopodia, using fascins and formins with integrated fluorescent tension sensors. This framework spanning from in vitro single filament to in vivo meso-scale actin networks will bring unprecedented insights into the role of actin bundles in filopodia mechanosensitivity.

 Publications

year authors and title journal last update
List of publications.
2018 Luyan Cao, Mikael Kerleau, Emiko L. Suzuki, Hugo Wioland, Sandy Jouet, Berengere Guichard, Martin Lenz, Guillaume Romet-Lemonne, Antoine Jegou
Modulation of formin processivity by profilin and mechanical tension
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.34176
eLife 7 2019-06-19
2017 Hugo Wioland, Berengere Guichard, Yosuke Senju, Sarah Myram, Pekka Lappalainen, Antoine Jégou, Guillaume Romet-Lemonne
ADF/Cofilin Accelerates Actin Dynamics by Severing Filaments and Promoting Their Depolymerization at Both Ends
published pages: 1956-1967.e7, ISSN: 0960-9822, DOI: 10.1016/j.cub.2017.05.048
Current Biology 27/13 2019-06-19
2016 Julien Pernier, Shashank Shekhar, Antoine Jegou, Bérengère Guichard, Marie-France Carlier
Profilin Interaction with Actin Filament Barbed End Controls Dynamic Instability, Capping, Branching, and Motility
published pages: 201-214, ISSN: 1534-5807, DOI: 10.1016/j.devcel.2015.12.024
Developmental Cell 36/2 2019-04-18
2016 Antoine Jégou, Guillaume Romet-Lemonne
Single Filaments to Reveal the Multiple Flavors of Actin
published pages: 2138-2146, ISSN: 0006-3495, DOI: 10.1016/j.bpj.2016.04.025
Biophysical Journal 110/10 2019-04-18
2018 Hugo Wioland, Antoine Jegou, Guillaume Romet-Lemonne
Quantitative Variations with pH of Actin Depolymerizing Factor/Cofilin’s Multiple Actions on Actin Filaments
published pages: 40-47, ISSN: 0006-2960, DOI: 10.1021/acs.biochem.8b01001
Biochemistry 58/1 2019-04-13
2019 Hugo Wioland, Antoine Jegou, Guillaume Romet-Lemonne
Torsional stress generated by ADF/cofilin on cross-linked actin filaments boosts their severing
published pages: 2595-2602, ISSN: 0027-8424, DOI: 10.1073/pnas.1812053116
Proceedings of the National Academy of Sciences 116/7 2019-04-13

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