Competition between Tropomyosin, Fimbrin, and ADF/Cofilin drives their sorting to distinct actin filament networks

  1. Jenna R Christensen
  2. Glen M Hocky
  3. Kaitlin E Homa
  4. Alisha N Morganthaler
  5. Sarah E Hitchcock-DeGregori
  6. Gregory A Voth
  7. David R Kovar  Is a corresponding author
  1. The University of Chicago, United States
  2. Rutgers University, United States

Abstract

The fission yeast actin cytoskeleton is an ideal, simplified system to investigate fundamental mechanisms behind cellular self-organization. By focusing on the stabilizing protein tropomyosin Cdc8, bundling protein fimbrin Fim1, and severing protein coffin Adf1, we examined how their pairwise and collective interactions with actin filaments regulate their activity and segregation to functionally diverse F-actin networks. Utilizing multi-color TIRF microscopy of in vitro reconstituted F-actin networks, we observed and characterized two distinct Cdc8 cables loading and spreading cooperatively on individual actin filaments. Furthermore, Cdc8, Fim1, and Adf1 all compete for association with F-actin by different mechanisms, and their cooperative association with actin filaments affects their ability to compete. Finally, competition between Fim1 and Adf1 for F-actin synergizes their activities, promoting rapid displacement of Cdc8 from a dense F-actin network. Our findings reveal that competitive and cooperative interactions between actin binding proteins help define their associations with different F-actin networks.

Article and author information

Author details

  1. Jenna R Christensen

    Molecular Genetics and Cell Biology, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Glen M Hocky

    Department of Chemistry, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5637-0698
  3. Kaitlin E Homa

    Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alisha N Morganthaler

    Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Sarah E Hitchcock-DeGregori

    Department of Pathology and Laboratory Medicine, Rutgers University, New Brunswick, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Gregory A Voth

    Department of Chemistry, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. David R Kovar

    Molecular Genetics and Cell Biology, Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States
    For correspondence
    drkovar@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5747-0949

Funding

National Institutes of Health (GM079265)

  • David R Kovar

American Cancer Society (RSG-11-126-01-CSM)

  • David R Kovar

National Science Foundation (DGE-1144082)

  • Jenna R Christensen

National Institutes of Health (T32 GM0071832)

  • Jenna R Christensen
  • Kaitlin E Homa

National Institutes of Health (F32 GM113415-01)

  • Glen M Hocky

National Institutes of Health (GM093965)

  • Sarah E Hitchcock-DeGregori

National Science Foundation (DMR-1420709)

  • Gregory A Voth
  • David R Kovar

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

Reviewing Editor

  1. Mohan K Balasubramanian, University of Warwick, United Kingdom

Publication history

  1. Received: November 10, 2016
  2. Accepted: March 9, 2017
  3. Accepted Manuscript published: March 10, 2017 (version 1)
  4. Version of Record published: April 25, 2017 (version 2)

Copyright

© 2017, Christensen 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. Jenna R Christensen
  2. Glen M Hocky
  3. Kaitlin E Homa
  4. Alisha N Morganthaler
  5. Sarah E Hitchcock-DeGregori
  6. Gregory A Voth
  7. David R Kovar
(2017)
Competition between Tropomyosin, Fimbrin, and ADF/Cofilin drives their sorting to distinct actin filament networks
eLife 6:e23152.
https://doi.org/10.7554/eLife.23152
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