ICK is essential for cell type‐specific ciliogenesis and the regulation of ciliary transport

Abstract

Cilia and flagella are formed and maintained by intraflagellar transport (IFT) and play important roles in sensing and moving across species. At the distal tip of the cilia/flagella, IFT complexes turn around to switch from anterograde to retrograde transport; however, the underlying regulatory mechanism is unclear. Here, we identified ICK localization at the tip of cilia as a regulator of ciliary transport. In ICK-deficient mice, we found ciliary defects in neuronal progenitor cells with Hedgehog signal defects. ICK-deficient cells formed cilia with mislocalized Hedgehog signaling components. Loss of ICK caused the accumulation of IFT-A, IFT-B, and BBSome components at the ciliary tips. In contrast, overexpression of ICK induced the strong accumulation of IFT-B, but not IFT-A or BBSome components at ciliary tips. In addition, ICK directly phosphorylated Kif3a, while inhibition of this Kif3a phosphorylation affected ciliary formation. Our results suggest that ICK is a Kif3a kinase and essential for proper ciliogenesis in development by regulating ciliary transport at the tip of cilia.

FLA8/KIF3B Phosphorylation Regulates Kinesin-II Interaction with IFT-B to Control IFT Entry and Turnaround

“…IFT172 in Chlamydomonas, BBSome, and IFT144 in C. elegans have been shown to be critical for this interaction (Pedersen et al, 2005;Wei et al, 2012). The induced accumulation of both IFT-A and IFT-B by depletion of CrCDPK1 (this work) or ICK (Chaya et al, 2014) demonstrates that this interaction is under regulatory control.…”

“…Therefore, FLA8 phosphorylation serves as a molecular switch to control loading and unloading of IFT particles. Interestingly, it has been shown recently that KIF3A phosphorylation regulates ciliogenesis (Chaya et al, 2014). However, no direct evidence has been presented for the involvement of KIF3A phosphorylation in IFT regulation.…”

“…Rather, it travels further, to the distal segment, indicating that DYF-5 regulates the interaction of kinesin-II with IFT particles (Burghoorn et al, 2007). It has been shown recently that KIF3A is phosphorylated by ICK and that either loss or overexpression of ICK causes the accumulation of IFT-B at the ciliary tip (Chaya et al, 2014).…”

“…The null mutant of LF2, a homolog of cell cycle-related kinase, exhibits unequal length of flagella with accumulation of IFT particles at the flagellar tip (Tam et al, 2007). A group of conserved mitogen-activated protein (MAP) kinase subfamily members, including Chlamydomonas LF4, worm DYF-5, and mammalian MAK and ICK, are involved in IFT regulation (Berman et al, 2003;Burghoorn et al, 2007;Chaya et al, 2014;Omori et al, 2010;Yang et al, 2013). An increased IFT injection rate is observed in the lf4 mutant (Ludington et al, 2013).…”

Loss of ift122, a Retrograde Intraflagellar Transport (IFT) Complex Component, Leads to Slow, Progressive Photoreceptor Degeneration Due to Inefficient Opsin Transport

“…Interestingly, a mutation of the nematode homolog of Mak, Dyf-5, affects the anterograde transport of IFT-A and -B proteins in sensory cilia (39). Recently, we showed that a paralog of Mak, ICK, regulates IFT turnaround at ciliary tips (40). It may be possible that ciliary kinases such as Mak and ICK are also involved in the regulation of IFT-A machinery by phosphorylation of these IFT components.…”