Profilin and formin constitute a pacemaker system for robust actin filament growth

  1. Johanna Funk
  2. Felipe Merino
  3. Larisa Venkova
  4. Lina Heydenreich
  5. Jan Kierfeld
  6. Pablo Vargas
  7. Stefan Raunser
  8. Matthieu Piel
  9. Peter Bieling  Is a corresponding author
  1. Max Planck Institute of Molecular Physiology, Germany
  2. Institut Curie, France
  3. TU Dortmund University, Germany

Abstract

The actin cytoskeleton drives many essential biological processes, from cell morphogenesis to motility. Assembly of functional actin networks requires control over the speed at which actin filaments grow. How this can be achieved at the high and variable levels of soluble actin subunits found in cells is unclear. Here we reconstitute assembly of mammalian, non-muscle actin filaments from physiological concentrations of profilin-actin. We discover that under these conditions, filament growth is limited by profilin dissociating from the filament end and the speed of elongation becomes insensitive to the concentration of soluble subunits. Profilin release can be directly promoted by formin actin polymerases even at saturating profilin-actin concentrations. We demonstrate that mammalian cells indeed operate at the limit to actin filament growth imposed by profilin and formins. Our results reveal how synergy between profilin and formins generates robust filament growth rates that are resilient to changes in the soluble subunit concentration.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Johanna Funk

    Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Felipe Merino

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4166-8747
  3. Larisa Venkova

    UMR 144, Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5721-7962
  4. Lina Heydenreich

    Physics Department, TU Dortmund University, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Jan Kierfeld

    Physics Department, TU Dortmund University, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4291-0638
  6. Pablo Vargas

    UMR 144, Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Stefan Raunser

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9373-3016
  8. Matthieu Piel

    UMR 144, Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Peter Bieling

    Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    For correspondence
    peter.bieling@mpi-dortmund.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7458-4358

Funding

Human Frontier Science Program (CDA00070/2017-2)

  • Johanna Funk
  • Peter Bieling

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

Reviewing Editor

  1. Pekka Lappalainen, University of Helsinki, Finland

Version history

  1. Received: August 8, 2019
  2. Accepted: October 24, 2019
  3. Accepted Manuscript published: October 24, 2019 (version 1)
  4. Version of Record published: November 20, 2019 (version 2)

Copyright

© 2019, Funk et al.

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.

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  1. Johanna Funk
  2. Felipe Merino
  3. Larisa Venkova
  4. Lina Heydenreich
  5. Jan Kierfeld
  6. Pablo Vargas
  7. Stefan Raunser
  8. Matthieu Piel
  9. Peter Bieling
(2019)
Profilin and formin constitute a pacemaker system for robust actin filament growth
eLife 8:e50963.
https://doi.org/10.7554/eLife.50963

Share this article

https://doi.org/10.7554/eLife.50963

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