Interplay between kinesin-1 and cortical dynein during axonal outgrowth and microtubule organization in Drosophila neurons

In this study, we investigated how microtubule motors organize microtubules in Drosophila neurons. We showed that, during the initial stages of axon outgrowth, microtubules display mixed polarity and minus-end-out microtubules push the tip of the axon, consistent with kinesin-1 driving outgrowth by...

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Main Authors: Urko del Castillo, Michael Winding, Wen Lu, Vladimir I Gelfand
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2015-11-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/10140
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spelling doaj-2f1c7c4131f6428abafa3950b78e11a82021-05-05T00:11:26ZengeLife Sciences Publications LtdeLife2050-084X2015-11-01410.7554/eLife.10140Interplay between kinesin-1 and cortical dynein during axonal outgrowth and microtubule organization in Drosophila neuronsUrko del Castillo0Michael Winding1Wen Lu2Vladimir I Gelfand3Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, United StatesDepartment of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, United StatesDepartment of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, United StatesDepartment of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, United StatesIn this study, we investigated how microtubule motors organize microtubules in Drosophila neurons. We showed that, during the initial stages of axon outgrowth, microtubules display mixed polarity and minus-end-out microtubules push the tip of the axon, consistent with kinesin-1 driving outgrowth by sliding antiparallel microtubules. At later stages, the microtubule orientation in the axon switches from mixed to uniform polarity with plus-end-out. Dynein knockdown prevents this rearrangement and results in microtubules of mixed orientation in axons and accumulation of microtubule minus-ends at axon tips. Microtubule reorganization requires recruitment of dynein to the actin cortex, as actin depolymerization phenocopies dynein depletion, and direct recruitment of dynein to the membrane bypasses the actin requirement. Our results show that cortical dynein slides ‘minus-end-out’ microtubules from the axon, generating uniform microtubule arrays. We speculate that differences in microtubule orientation between axons and dendrites could be dictated by differential activity of cortical dynein.https://elifesciences.org/articles/10140microtubulesneuronaxonskinesindyneinactin
collection DOAJ
language English
format Article
sources DOAJ
author Urko del Castillo
Michael Winding
Wen Lu
Vladimir I Gelfand
spellingShingle Urko del Castillo
Michael Winding
Wen Lu
Vladimir I Gelfand
Interplay between kinesin-1 and cortical dynein during axonal outgrowth and microtubule organization in Drosophila neurons
eLife
microtubules
neuron
axons
kinesin
dynein
actin
author_facet Urko del Castillo
Michael Winding
Wen Lu
Vladimir I Gelfand
author_sort Urko del Castillo
title Interplay between kinesin-1 and cortical dynein during axonal outgrowth and microtubule organization in Drosophila neurons
title_short Interplay between kinesin-1 and cortical dynein during axonal outgrowth and microtubule organization in Drosophila neurons
title_full Interplay between kinesin-1 and cortical dynein during axonal outgrowth and microtubule organization in Drosophila neurons
title_fullStr Interplay between kinesin-1 and cortical dynein during axonal outgrowth and microtubule organization in Drosophila neurons
title_full_unstemmed Interplay between kinesin-1 and cortical dynein during axonal outgrowth and microtubule organization in Drosophila neurons
title_sort interplay between kinesin-1 and cortical dynein during axonal outgrowth and microtubule organization in drosophila neurons
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2015-11-01
description In this study, we investigated how microtubule motors organize microtubules in Drosophila neurons. We showed that, during the initial stages of axon outgrowth, microtubules display mixed polarity and minus-end-out microtubules push the tip of the axon, consistent with kinesin-1 driving outgrowth by sliding antiparallel microtubules. At later stages, the microtubule orientation in the axon switches from mixed to uniform polarity with plus-end-out. Dynein knockdown prevents this rearrangement and results in microtubules of mixed orientation in axons and accumulation of microtubule minus-ends at axon tips. Microtubule reorganization requires recruitment of dynein to the actin cortex, as actin depolymerization phenocopies dynein depletion, and direct recruitment of dynein to the membrane bypasses the actin requirement. Our results show that cortical dynein slides ‘minus-end-out’ microtubules from the axon, generating uniform microtubule arrays. We speculate that differences in microtubule orientation between axons and dendrites could be dictated by differential activity of cortical dynein.
topic microtubules
neuron
axons
kinesin
dynein
actin
url https://elifesciences.org/articles/10140
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