Ciliary entry of the kinesin-2 motor KIF17 is regulated by importin-β2 and RanGTP. Nat Cell Biol

Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Nature Cell Biology (Impact Factor: 20.06). 07/2010; 12(7):703-10. DOI: 10.1038/ncb2073
Source: PubMed

ABSTRACT The biogenesis, maintenance and function of primary cilia are controlled through intraflagellar transport (IFT) driven by two kinesin-2 family members, the heterotrimeric KIF3A/KIF3B/KAP complex and the homodimeric KIF17 motor. How these motors and their cargoes gain access to the ciliary compartment is poorly understood. Here, we identify a ciliary localization signal (CLS) in the KIF17 tail domain that is necessary and sufficient for ciliary targeting. Similarities between the CLS and classic nuclear localization signals (NLSs) suggest that similar mechanisms regulate nuclear and ciliary import. We hypothesize that ciliary targeting of KIF17 is regulated by a ciliary-cytoplasmic gradient of the small GTPase Ran, with high levels of GTP-bound Ran (RanGTP) in the cilium. Consistent with this, cytoplasmic expression of GTP-locked Ran(G19V) disrupts the gradient and abolishes ciliary entry of KIF17. Furthermore, KIF17 interacts with the nuclear import protein importin-beta2 in a manner dependent on the CLS and inhibited by RanGTP. We propose that Ran has a global role in regulating cellular compartmentalization by controlling the shuttling of cytoplasmic proteins into nuclear and ciliary compartments.

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Available from: Paul Jenkins, Aug 16, 2015
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    • "These results can potentially be explained by effects of Ran-GTP on the balance between anterograde and retrograde trafficking of Kif17 along ciliary microtubules or by changes in microtubule dynamics, which Ran-GTP is known to regulate (Keryer et al., 2003; Mishra et al., 2010; Fan et al., 2011; Halpin et al., 2011). Together with the fact that a GDP-locked Ran mutant that disrupts nucleocytoplasmic transport does not affect the ciliary localization of Kif17, these data suggest that the ciliary functions of Ran differ from those in nucleocytoplasmic transport (Dishinger et al., 2010). Future experiments that address how Ran-GTP levels in the cilium are controlled, the function of nucleoporins at the ciliary base (Kee et al., 2012), and whether exportins regulate ciliary exit will clarify the extent to which trafficking through the ciliary base and nuclear pores resemble each other. "
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