Growth cone-localized microtubule organizing center establishes microtubule orientation in dendrites
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.
All data generated or analyzed during this study are included in the manuscript and supporting files.
Article and author information
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.
- Jens Lüders, Institute for Research in Biomedicine, Spain
- Received: March 2, 2020
- Accepted: July 9, 2020
- Accepted Manuscript published: July 13, 2020 (version 1)
- Version of Record published: July 22, 2020 (version 2)
© 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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