Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion

  1. Julia Damiano- Guercio
  2. Laëtitia Kurzawa
  3. Jan Mueller
  4. Georgi Dimchev
  5. Matthias Schaks
  6. Maria Nemethova
  7. Thomas Pokrant
  8. Stefan Brühmann
  9. Joern Linkner
  10. Laurent Blanchoin
  11. Michael Sixt
  12. Klemens Rottner
  13. Jan Faix  Is a corresponding author
  1. Hannover Medical School, Germany
  2. CytoMorphoLab, France
  3. Institute of Science and Technology Austria (IST Austria), Austria
  4. Technische Universität Braunschweig, Germany
  5. Interdisciplinary Research Institute Grenoble, France

Abstract

Cell migration entails networks and bundles of actin filaments termed lamellipodia and microspikes or filopodia, respectively, as well as focal adhesions, all of which recruit Ena/VASP family members hitherto thought to antagonize efficient cell motility. However, we find these proteins to act as positive regulators of migration in different murine cell lines. CRISPR/Cas9-mediated loss of Ena/VASP proteins reduced lamellipodial actin assembly and perturbed lamellipodial architecture, as evidenced by changed network geometry as well as reduction of filament length and number that was accompanied by abnormal Arp2/3 complex and heterodimeric capping protein accumulation. Loss of Ena/VASP function also abolished the formation of microspikes normally embedded in lamellipodia, but not of filopodia capable of emanating without lamellipodia. Ena/VASP-deficiency also impaired integrin-mediated adhesion accompanied by reduced traction forces exerted through these structures. Our data thus uncover novel Ena/VASP functions of these actin polymerases that are fully consistent with their promotion of cell migration.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for all Figures.

Article and author information

Author details

  1. Julia Damiano- Guercio

    Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Laëtitia Kurzawa

    Integrative Structural and Cellular Biology Department, CytoMorphoLab, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Jan Mueller

    Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
  4. Georgi Dimchev

    Division of Molecular Cell Biology, Technische Universität Braunschweig, Braunschweig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Matthias Schaks

    Division of Molecular Cell Biology, Technische Universität Braunschweig, Braunschweig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Maria Nemethova

    Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
  7. Thomas Pokrant

    Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Stefan Brühmann

    Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Joern Linkner

    Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Laurent Blanchoin

    Laboratoire de Physiologie Cellulaire & Végétale, Interdisciplinary Research Institute Grenoble, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8146-9254
  11. Michael Sixt

    Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6620-9179
  12. Klemens Rottner

    Zoological Institute - Division of Molecular Cell Biology, Technische Universität Braunschweig, Braunschweig, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4244-4198
  13. Jan Faix

    Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany
    For correspondence
    faix.jan@mh-hannover.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1803-9192

Funding

Deutsche Forschungsgemeinschaft (FA 330/11-1)

  • Jan Faix

H2020 European Research Council (AAA 741773)

  • Laurent Blanchoin

H2020 European Research Council (CoG 724373)

  • Michael Sixt

Deutsche Forschungsgemeinschaft (RO2414/5-1)

  • Klemens Rottner

Technische Universität Braunschweig (GRK2223/1)

  • Klemens Rottner

Austrian Science Fund

  • Michael Sixt

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

Publication history

  1. Received: January 21, 2020
  2. Accepted: May 8, 2020
  3. Accepted Manuscript published: May 11, 2020 (version 1)
  4. Version of Record published: May 20, 2020 (version 2)

Copyright

© 2020, Damiano- Guercio 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. Julia Damiano- Guercio
  2. Laëtitia Kurzawa
  3. Jan Mueller
  4. Georgi Dimchev
  5. Matthias Schaks
  6. Maria Nemethova
  7. Thomas Pokrant
  8. Stefan Brühmann
  9. Joern Linkner
  10. Laurent Blanchoin
  11. Michael Sixt
  12. Klemens Rottner
  13. Jan Faix
(2020)
Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion
eLife 9:e55351.
https://doi.org/10.7554/eLife.55351
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