Editors' ChoiceCilia

IP6 Got Rhythm?

Science's STKE  18 Dec 2007:
Vol. 2007, Issue 417, pp. tw455
DOI: 10.1126/stke.4172007tw455

Motile cilia are plasma membrane projections that contain a central core of microtubules whose movement relative to each other contributes to ciliary beating. The left-right body patterning of developing embryos is thought to result from cilia-dependent differential distribution of morphogens. Knockout of inositol 1,3,4,5,6-pentakisphosphate (IP5) 2-kinase (Ipk1), the enzyme that synthesizes IP6, in zebrafish embryos results in defective left-right positioning of organs, although the mechanism involved is unknown. Sarmah et al. extended this work and knocked down expression of ipk1 in zebrafish by injecting embryos with an antisense morpholino oligonucleotide (MO) targeted to ipk1 mRNA (ipk1MO1 embryos). The Kupffer’s vesicle (KV) is the organ that initiates left-right organ placement in the zebrafish. The authors found that whereas KV cilia from wild-type embryos beat with a regular frequency in a counterclockwise direction, those from ipk1MO1 embryos vibrated without a defined direction of motion. Furthermore, immunocytochemical analyses revealed that cilia in ipk1MO1 embryos were shorter than those in wild-type embryos. Although the ectopic expression in ipk1MO1 embryos of Ipk1 resulted in the rescue of ciliary length and motion, that of a catalytically inactive mutant of Ipk1 did not. Fluorescence microscopy showed that Ipk1 was localized to centrosomes in the basal bodies of cilia in wild-type embryos. Transmission electron microscopy demonstrated that the organization of microtubules in the cilia from ipk1MO1 embryos was similar to that in wild-type embryos. However, the anterograde microtubule-dependent movement of melanosomes (pigmented vesicles), which is mediated by kinesin proteins, was much slower in ipk1MO1 cilia than in wild-type cilia. Together these data implicate Ipk1, and potentially its product IP6, in the maintenance of cilia length and the regulation of ciliary motion.

B. Sarmah, V. P. Winfrey, G. E. Olson, B. Appel, S. R. Wente, A role for the inositol kinase Ipk1 in ciliary beating and length maintenance. Proc. Natl. Acad. Sci. U.S.A. 104, 19843-19848 (2007). [Abstract] [Full Text]