1. Structural Biology and Molecular Biophysics
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Recruitment of two dyneins to an mRNA-dependent Bicaudal D transport complex

  1. Thomas E Sladewski
  2. Neil Billington
  3. M Yusuf Ali
  4. Carol S Bookwalter
  5. Hailong Lu
  6. Elena B Krementsova
  7. Trina A Schroer
  8. Kathleen M Trybus  Is a corresponding author
  1. University of Vermont, United States
  2. National Heart, Lung and Blood Institute, National Institutes of Health, United States
  3. Johns Hopkins University, United States
Research Article
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Cite this article as: eLife 2018;7:e36306 doi: 10.7554/eLife.36306

Abstract

We investigated the role of full-length Drosophila Bicaudal D (BicD) binding partners in dynein-dynactin activation for mRNA transport on microtubules. Full-length BicD robustly activated dynein-dynactin motility only when both the mRNA binding protein Egalitarian (Egl) and K10 mRNA cargo were present, and electron microscopy showed that both Egl and mRNA were needed to disrupt a looped, auto-inhibited BicD conformation. BicD can recruit two dimeric dyneins, resulting in faster speeds and longer runs than with one dynein. Moving complexes predominantly contained two Egl molecules and one K10 mRNA. This mRNA-bound configuration makes Egl bivalent, likely enhancing its avidity for BicD and thus its ability to disrupt BicD auto-inhibition. Consistent with this idea, artificially dimerized Egl activates dynein-dynactin-BicD in the absence of mRNA. The ability of mRNA cargo to orchestrate the activation of the mRNP (messenger ribonucleotide protein) complex is an elegant way to ensure that only cargo-bound motors are motile.

Data availability

Data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been included for Figures 1, 4-10.

Article and author information

Author details

  1. Thomas E Sladewski

    Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Neil Billington

    Laboratory of Physiology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2306-0228
  3. M Yusuf Ali

    Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Carol S Bookwalter

    Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Hailong Lu

    Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Elena B Krementsova

    Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Trina A Schroer

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5065-1835
  8. Kathleen M Trybus

    Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, United States
    For correspondence
    kathleen.trybus@uvm.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5583-8500

Funding

National Institutes of Health (GM078097)

  • Kathleen M Trybus

American Heart Association (12SDG11930002)

  • M Yusuf Ali

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

Reviewing Editor

  1. Andrea Musacchio, Max Planck Institute of Molecular Physiology, Germany

Publication history

  1. Received: March 1, 2018
  2. Accepted: June 23, 2018
  3. Accepted Manuscript published: June 26, 2018 (version 1)
  4. Version of Record published: July 23, 2018 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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