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Geometrical Constraints Greatly Hinder Formin mDia1 Activity

[Image: see text] Formins are one of the central players in the assembly of most actin networks in cells. The sensitivity of these processive molecular machines to mechanical tension is now well established. However, how the activity of formins is affected by geometrical constraints related to netwo...

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Autores principales: Suzuki, Emiko L., Chikireddy, Jahnavi, Dmitrieff, Serge, Guichard, Bérengère, Romet-Lemonne, Guillaume, Jégou, Antoine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086397/
https://www.ncbi.nlm.nih.gov/pubmed/31797667
http://dx.doi.org/10.1021/acs.nanolett.9b02241
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author Suzuki, Emiko L.
Chikireddy, Jahnavi
Dmitrieff, Serge
Guichard, Bérengère
Romet-Lemonne, Guillaume
Jégou, Antoine
author_facet Suzuki, Emiko L.
Chikireddy, Jahnavi
Dmitrieff, Serge
Guichard, Bérengère
Romet-Lemonne, Guillaume
Jégou, Antoine
author_sort Suzuki, Emiko L.
collection PubMed
description [Image: see text] Formins are one of the central players in the assembly of most actin networks in cells. The sensitivity of these processive molecular machines to mechanical tension is now well established. However, how the activity of formins is affected by geometrical constraints related to network architecture, such as filament cross-linking and formin spatial confinement, remains largely unknown. Combining microfluidics and micropatterning, we reconstituted in vitro mDia1 formin-elongated filament bundles induced by fascin, with different geometrical constraints on the formins, and measured the impact of these constraints on formin elongation rate and processivity. When filaments are not bundled, the anchoring details of formins have only a mild impact on their processivity and do not affect their elongation rate. When formins are unanchored, we show that filament bundling by fascin reduces both their elongation rate and their processivity. Strikingly, when filaments elongated by surface-anchored formins are cross-linked together, formin elongation rate immediately decreases and processivity is reduced up to 24-fold depending on the cumulative impact of formin rotational and translational freedom. Our results reveal an unexpected crosstalk between the constraints at the filament and the formin levels. We anticipate that in cells the molecular details of formin anchoring to the plasma membrane strongly modulate formin activity at actin filament barbed ends.
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spelling pubmed-70863972020-03-24 Geometrical Constraints Greatly Hinder Formin mDia1 Activity Suzuki, Emiko L. Chikireddy, Jahnavi Dmitrieff, Serge Guichard, Bérengère Romet-Lemonne, Guillaume Jégou, Antoine Nano Lett [Image: see text] Formins are one of the central players in the assembly of most actin networks in cells. The sensitivity of these processive molecular machines to mechanical tension is now well established. However, how the activity of formins is affected by geometrical constraints related to network architecture, such as filament cross-linking and formin spatial confinement, remains largely unknown. Combining microfluidics and micropatterning, we reconstituted in vitro mDia1 formin-elongated filament bundles induced by fascin, with different geometrical constraints on the formins, and measured the impact of these constraints on formin elongation rate and processivity. When filaments are not bundled, the anchoring details of formins have only a mild impact on their processivity and do not affect their elongation rate. When formins are unanchored, we show that filament bundling by fascin reduces both their elongation rate and their processivity. Strikingly, when filaments elongated by surface-anchored formins are cross-linked together, formin elongation rate immediately decreases and processivity is reduced up to 24-fold depending on the cumulative impact of formin rotational and translational freedom. Our results reveal an unexpected crosstalk between the constraints at the filament and the formin levels. We anticipate that in cells the molecular details of formin anchoring to the plasma membrane strongly modulate formin activity at actin filament barbed ends. American Chemical Society 2019-12-04 2020-01-08 /pmc/articles/PMC7086397/ /pubmed/31797667 http://dx.doi.org/10.1021/acs.nanolett.9b02241 Text en Copyright © 2019 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.
spellingShingle Suzuki, Emiko L.
Chikireddy, Jahnavi
Dmitrieff, Serge
Guichard, Bérengère
Romet-Lemonne, Guillaume
Jégou, Antoine
Geometrical Constraints Greatly Hinder Formin mDia1 Activity
title Geometrical Constraints Greatly Hinder Formin mDia1 Activity
title_full Geometrical Constraints Greatly Hinder Formin mDia1 Activity
title_fullStr Geometrical Constraints Greatly Hinder Formin mDia1 Activity
title_full_unstemmed Geometrical Constraints Greatly Hinder Formin mDia1 Activity
title_short Geometrical Constraints Greatly Hinder Formin mDia1 Activity
title_sort geometrical constraints greatly hinder formin mdia1 activity
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086397/
https://www.ncbi.nlm.nih.gov/pubmed/31797667
http://dx.doi.org/10.1021/acs.nanolett.9b02241
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