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 downregulated in neurons to control neurite outgrowth, and establish parallels between microtubule-sliding in mitosis and post-mitotic neurons.
Original language | English (US) |
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Journal | eLife |
Volume | 9 |
DOIs | |
State | Published - Feb 5 2020 |
Keywords
- D. melanogaster
- Drosophila
- Pavarotti
- Tricornered kinase
- cell biology
- kinesin
- microtubules
- neurons
- neuroscience
ASJC Scopus subject areas
- General Neuroscience
- General Immunology and Microbiology
- General Biochemistry, Genetics and Molecular Biology