Primary cilium is an antenna-like sensory organelle, protruding from the surface of most human cells. Its assembly is templated by the mother centriole-derived basal body, which serves as a base for outgrowth of the ciliary axoneme. Primary cilia contain components of several signaling pathways, and, in turn, have important functions in human development and diseases. Their assembly and disassembly seem to be tightly coupled to the cell cycle progression. However, the identity of the responsible regulators, their mutual interactions, and the extend of the crosstalk between cilia and the cell cycle machinery, are only beginning to emerge. In our work, published in the Journal of the cell biology we have identified protein KIF14 as a new element linking the cell cycle and cilium formation. KIF14 is kinesin - a molecular motor regulating later stages of cell division. In this work we found that KIF14, beside participating in cell division, actually localizes to primary cilia to regulate their assembly, maintenance, and function. Specifically, we found that depletion of KIF14 by RNAi impairs dynamics of primary cilium elongation and disrupts the localization of a number of key components implicated in the cilium assembly pathway, namely basal body proteins SCLT1 and FBF1, and components intraflagellar transport. We identified deregulated Aurora A activity as a mechanism responsible for these defects in KIF14 depleted cells. In addition, we found that primary cilia in KIF14-depleted cells are defective in response to Hedgehog pathway activation, independently of the effects of Aurora A. In sum, our data point to KIF14 as a critical node connecting cell cycle machinery, effective ciliogenesis, and Hedgehog signaling.
This work, supervised by Dr. Lukáš Čajánek, was primarily carried out by PhD. student Petra Pejšková at the Department of Histology and Embryology, Faculty of Medicine at Masaryk University in Brno, Czech Republic, in collaboration with Dr. Alexandre Benmerah from Laboratory of Hereditary Kidney Diseases at the Imagine Institute, Paris University, France.