Worm orthologues of cytokinesis-associated proteins CIT and ASPM regulate neuronal microtubule dynamics and polarity in C. elegans.

The polarized architecture of neurons is intricately associated with the modulation of microtubule dynamics. Over the years, several microtubule-associated factors that regulate neuronal polarity have been identified. However, the precise details of how microtubule arrangement and stability are established in axons and dendrites are not clearly understood. To uncover the relevant factors involved in the biological pathways governing microtubule regulation in neurons, we conducted a suppressor screen using the neuronal ectopic extension phenotype caused by the loss of the kinesin-13 family microtubule depolymerizing protein KLP-7 in C. elegans. Interestingly, apart from eleven variants of α (mec-12) and β (mec-7) tubulins, we isolated a variant of cytokinesis-associated protein, W02B8.2/citk-1, the suggested kinase-less orthologue of mammalian citron-rho interacting kinase (CIT). Little is known about the role of CIT in microtubule regulation in post-mitotic neurons. In this study, we found that the kinase-less worm orthologues of CIT, citk-1 and citk-2, redundantly modulate microtubule stability in the axon-like anterior process and maintain the population of plus-end-out microtubules in the dendrite-like posterior process of the PLM mechanosensory neurons in a cell-autonomous manner. In the absence of citk-1 and citk-2, PLM neurons exhibit variable morphological defects, including neurite growth and synaptic branch defects. Moreover, we find that CITK-1/2 work in the same genetic pathway as ASPM-1 (the worm homolog of mammalian ASPM (abnormal spindle-like microcephaly-associated protein)) to modulate plus-end dynamics of microtubules in PLM neurons. Our findings suggest that the cytokinesis-associated CITK-1/2 and ASPM-1 have non-mitotic roles in regulation of microtubules in differentiated PLM neurons.