Growth cone-localized microtubule organizing center establishes microtubule orientation in dendrites

  1. Xing Liang
  2. Marcela Kokes
  3. Richard D Fetter
  4. Maria Danielle Sallee
  5. Adrian W Moore
  6. Jessica L Feldman  Is a corresponding author
  7. Kang Shen  Is a corresponding author
  1. Stanford University, United States
  2. Howard Hughes Medical Institute, United States
  3. Riken Brain Science Institute, Japan
  4. Howard Hughes Medical Institute, Stanford University, United States

Abstract

A polarized arrangement of neuronal microtubule arrays is the foundation of membrane trafficking and subcellular compartmentalization. Conserved among both invertebrates and vertebrates, axons contain exclusively 'plus-end-out' microtubules while dendrites contain a high percentage of 'minus-end-out' microtubules, the origins of which have been a mystery. Here we show that in Caenorhabditis elegans the dendritic growth cone contains a non-centrosomal microtubule organizing center, which generates minus-end-out microtubules along outgrowing dendrites and plus-end-out microtubules in the growth cone. RAB-11-positive endosomes accumulate in this region and co-migrate with the microtubule nucleation complex γ-TuRC. The MTOC tracks the extending growth cone by kinesin-1/UNC-116-mediated endosome movements on distal plus-end-out microtubules and dynein clusters this advancing MTOC. Critically, perturbation of the function or localization of the MTOC causes reversed microtubule polarity in dendrites. These findings unveil the endosome-localized dendritic MTOC as a critical organelle for establishing axon-dendrite polarity.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Xing Liang

    Biology, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  2. Marcela Kokes

    Biology, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  3. Richard D Fetter

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1558-100X
  4. Maria Danielle Sallee

    Biology, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  5. Adrian W Moore

    Riken Brain Science Institute, Wako, Japan
    Competing interests
    No competing interests declared.
  6. Jessica L Feldman

    Biology, Stanford University, Stanford, United States
    For correspondence
    feldmanj@stanford.edu
    Competing interests
    No competing interests declared.
  7. Kang Shen

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    For correspondence
    kangshen@stanford.edu
    Competing interests
    Kang Shen, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4059-8249

Funding

Howard Hughes Medical Institute

  • Kang Shen

National Institutes of Health (research project,NS082208)

  • Kang Shen

National Institutes of Health (NIH New Innovator Award,DP2GM119136-01)

  • Jessica L Feldman

National Institutes of Health (NIGMS NIH award F32GM120913-01)

  • Maria Danielle Sallee

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

Reviewing Editor

  1. Jens Lüders, Institute for Research in Biomedicine, Spain

Version history

  1. Received: March 2, 2020
  2. Accepted: July 9, 2020
  3. Accepted Manuscript published: July 13, 2020 (version 1)
  4. Version of Record published: July 22, 2020 (version 2)

Copyright

© 2020, Liang 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. Xing Liang
  2. Marcela Kokes
  3. Richard D Fetter
  4. Maria Danielle Sallee
  5. Adrian W Moore
  6. Jessica L Feldman
  7. Kang Shen
(2020)
Growth cone-localized microtubule organizing center establishes microtubule orientation in dendrites
eLife 9:e56547.
https://doi.org/10.7554/eLife.56547

Share this article

https://doi.org/10.7554/eLife.56547

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