A role for the inositol kinase Ipk1 in ciliary beating and length maintenance

doi:10.1073/pnas.0706934104

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A role for the inositol kinase Ipk1 in ciliary beating and length maintenance

Bhaskarjyoti Sarmah^*, Virginia P. Winfrey^*, Gary E. Olson^*, Bruce Appel, and Susan R. Wente^*^,

*Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232-8240; and Department of Biological Sciences, Vanderbilt University, Nashville, TN 37232

Edited by Philip W. Majerus, Washington University School of Medicine, St. Louis, MO, and approved October 23, 2007

Received for publication July 24, 2007.

Abstract: Cilia project from cells as membranous extensions, with microtubulestructural cores assembling from basal bodies by intraflagellartransport (IFT). Here, we report a ciliary role for the inositol1,3,4,5,6-pentakisphosphate 2-kinase (Ipk1) that generates inositolhexakisphosphate. In zebrafish embryos, reducing Ipk1 levelsinhibited ciliary beating in Kupffer's vesicle and decreasedciliary length in the spinal canal, pronephric ducts, and Kupffer'svesicle. Electron microscopy showed that ciliary axonemal structureswere not grossly altered. However, coincident knockdown of Ipk1and IFT88 or IFT57 had synergistic perturbations. With GFP-Ipk1enriched in centrosomes and basal bodies, we propose that Ipk1plays a previously uncharacterized role in ciliary function.

Key Words: cilia • inositol hexakisphosphate • kidney development • left–right asymmetry • zebrafish

Author contributions: B.S., G.E.O., B.A., and S.R.W. designedresearch; B.S., V.P.W., and G.E.O. performed research; B.S.contributed new reagents/analytic tools; B.S., V.P.W., G.E.O.,B.A., and S.R.W. analyzed data; and B.S., G.E.O., B.A., andS.R.W. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/cgi/content/full/0706934104/DC1.

To whom correspondence should be addressed at: Department of Cell and Developmental Biology, Vanderbilt University Medical Center, U-3209 MRBIII, Nashville, TN 37232-8240. E-mail: susan.wente{at}vanderbilt.edu

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