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Ser/Thr kinase Trc controls neurite outgrowth in Drosophila by modulating microtubule-microtubule sliding

  1. Rosalind Norkett
  2. Urko del Castillo
  3. Wen Lu
  4. Vladimir I Gelfand  Is a corresponding author
  1. Northwestern University, United States
Research Article
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Cite this article as: eLife 2020;9:e52009 doi: 10.7554/eLife.52009

Abstract

Correct neuronal development requires tailored neurite outgrowth. Neurite outgrowth is driven in part by microtubule-sliding – the transport of microtubules along each other. We have recently demonstrated that a 'mitotic' kinesin-6 (Pavarotti in Drosophila) effectively inhibits microtubule-sliding and neurite outgrowth. However, mechanisms regulating Pavarotti itself in interphase cells and specifically in neurite outgrowth are unknown. Here, we use a combination of live imaging and biochemical methods to show that the inhibition of microtubule-sliding by Pavarotti is controlled by phosphorylation. We identify the Ser/Thr NDR kinase Tricornered (Trc) as a Pavarotti-dependent regulator of microtubule sliding in neurons. Further, we show that Trc-mediated phosphorylation of Pavarotti promotes its interaction with 14-3-3 proteins. Loss of 14-3-3 prevents Pavarotti from associating with microtubules. Thus, we propose a pathway by which microtubule-sliding can be up or down regulated in neurons to control neurite outgrowth, and establish parallels between microtubule-sliding in mitosis and post-mitotic neurons.

Article and author information

Author details

  1. Rosalind Norkett

    Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Urko del Castillo

    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Wen Lu

    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Vladimir I Gelfand

    Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, United States
    For correspondence
    vgelfand@northwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6361-2798

Funding

National Institutes of Health (R01 GM052111)

  • Vladimir I Gelfand

National Institutes of Health (R35 GM131752)

  • Vladimir I Gelfand

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

Reviewing Editor

  1. Jennifer G. DeLuca, Colorado State University, United States

Publication history

  1. Received: September 19, 2019
  2. Accepted: February 5, 2020
  3. Accepted Manuscript published: February 5, 2020 (version 1)
  4. Version of Record published: February 14, 2020 (version 2)

Copyright

© 2020, Norkett 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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