Growth cone-localized microtubule organizing center establishes microtubule orientation in dendrites
- Stanford University, United States
- Howard Hughes Medical Institute, United States
- Riken Brain Science Institute, Japan
- 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
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.
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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Growth cone-localized microtubule organizing center establishes microtubule orientation in dendrites
eLife 9:e56547.
https://doi.org/10.7554/eLife.56547
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