@article {Huang562272, author = {Huang, Shengping and Avasthi, Prachee}, title = {RanGTP regulates cilium formation and ciliary trafficking of a kinesin-II subunit independent of its nuclear functions}, elocation-id = {562272}, year = {2019}, doi = {10.1101/562272}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Kinesin is part of the microtubule (MT)-binding motor protein superfamily, which exerts crucial functions in cell division and intracellular transport in different organelles. The heterotrimeric kinesin-II, consisting of the kinesin like protein KIF3A/3B heterodimer and kinesin-associated protein KAP3, is highly conserved across species from the green alga Chlamydomonas to humans. It plays diverse roles in cargo transport including anterograde (base to tip) trafficking in cilium. However, the molecular determinants mediating trafficking of heterotrimeric kinesin-II itself is poorly understood. Using the unicellular eukaryote Chlamydomonas and mammalian cells, we show that RanGTP regulates ciliary trafficking of KAP3. We found the armadillo repeat region 6-9 (ARM6-9) of KAP3, required for its nuclear translocation, is sufficient for its targeting to the ciliary base. Given that KAP3 is essential for cilia formation and the emerging roles of RanGTP/importin β in ciliary protein targeting, we further investigate the effect of RanGTP in cilium length regulation in these two different systems. We demonstrate that precise control of RanGTP levels, revealed by different Ran mutants, is crucial for cilium formation and maintenance. Most importantly, we were able to segregate RanGTP regulation of ciliary protein incorporation from of its nuclear roles. Our work provides important support for the model that nuclear import mechanisms have been coopted for independent roles in ciliary import.}, URL = {https://www.biorxiv.org/content/early/2019/04/19/562272}, eprint = {https://www.biorxiv.org/content/early/2019/04/19/562272.full.pdf}, journal = {bioRxiv} }