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

Correct neuronal development requires tailored neurite outgrowth. Neurite outgrowth is driven by microtubule sliding – the transport of microtubules along each other. We have recently demonstrated that a “mitotic” kinesin-6 (Pavarotti in Drosophila) inhibits microtubule-sliding and neurite outgrowth. However, mechanisms of Pavarotti regulation in interphase cells and specifically in neurite outgrowth are unknown. We use live imaging and biochemical analysis 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. 14-3-3 binding is necessary for Pavarotti to interact with microtubules and inhibit sliding. 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.