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

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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.

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

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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.
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.
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.
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.

"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.

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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.