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.
Highlights
In order to communicate, neurons must develop an extensive and precisely regulated network of axons and dendrites, collectively called neurites
Based on preliminary experiments we chose to focus on the NDR kinase Trc
The kinase Trc inhibits this process by phosphorylation of Pavarotti
Summary
Neurons must develop an extensive and precisely regulated network of axons and dendrites, collectively called neurites. Neurons are exceptionally dependent on microtubules for long range transport of cargo. Microtubule organization is essential for powering initial neurite outgrowth (Kapitein and Hoogenraad, 2015; Lu et al, 2013; Winding et al, 2016). In order to drive initial neurite outgrowth, microtubules themselves become the cargo and are transported relative to each other by molecular motors – a process known as microtubule sliding. In cultured Drosophila neurons, microtubules can be seen pushing the plasma membrane at the tips of growing processes (del Castillo et al, 2015; Lu et al, 2013)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
