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Published online
doi:10.1083/jcb.200703047
The Journal of Cell Biology, Vol. 178, No. 3, 363-369
The Rockefeller University Press, 0021-9525 $30.00
© Yoshimura et al.
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Functional dissection of Rab GTPases involved in primary cilium formation



Shin-ichiro Yoshimura1,2, Johannes Egerer2, Evelyn Fuchs2, Alexander K. Haas2, and Francis A. Barr1,2

1 University of Liverpool Cancer Research Centre, Liverpool L3 9TA, England, UK
2 Department of Cell Biology, Max Planck Institute of Biochemistry, Martinsried, 82152 Germany

Correspondence to Francis Barr: fabarr{at}liverpool.ac.uk

Primary cilia are sensory structures involved in morphogen signalling during development, liquid flow in the kidney, mechanosensation, sight, and smell (Badano, J.L., N. Mitsuma, P.L. Beales, and N. Katsanis. 2006. Annu. Rev. Genomics Hum. Genet. 7:125–148; Singla, V., and J.F. Reiter. 2006. Science. 313:629–633.). Mutations that affect primary cilia are responsible for several diseases, including neural tube defects, polycystic kidney disease, retinal degeneration, and cancers (Badano et al., 2006; Singla and Reiter, 2006). Primary cilia formation and function requires tight integration of the microtubule cytoskeleton with membrane trafficking (Singla and Reiter, 2006), and this is poorly understood. We show that the Rab GTPase membrane trafficking regulators Rab8a, -17, and -23, and their cognate GTPase-activating proteins (GAPs), XM_037557, TBC1D7, and EVI5like, are involved in primary cilia formation. However, other human Rabs and GAPs are not. Additionally, Rab8a specifically interacts with cenexin/ODF2, a basal body and microtubule binding protein required for cilium biogenesis (Ishikawa, H., A. Kubo, S. Tsukita, and S. Tsukita. 2005. Nat. Cell Biol. 7:517–524), and is the sole Rab enriched at primary cilia. These findings provide a basis for understanding how specific membrane trafficking pathways cooperate with the microtubule cytoskeleton to give rise to the primary cilia.

Abbreviations used in this paper: GAP, GTPase-activating protein; IFT, intraflagellar transport complex.


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