Recruitment of two dyneins to an mRNA-dependent Bicaudal D transport complex
- University of Vermont, United States
- National Heart, Lung and Blood Institute, National Institutes of Health, United States
- Johns Hopkins University, United States
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.
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Author details
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.
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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Recruitment of two dyneins to an mRNA-dependent Bicaudal D transport complex
eLife 7:e36306.
https://doi.org/10.7554/eLife.36306
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