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bioRxiv · 10.1101/2023.11.09.564704

Distinct functions of the kinesin-9 family in mammalian motile cilia

Fang, C.·Pan, X.·Li, D.·Chen, Y.·Li, L.·Gao, Q.·Zhu, X.·Yan, X.
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Abstract

Ciliary beat and intraflagellar transport (IFT) depend on dynein and kinesin motors. Kinesin-9 family members Kif6 and Kif9 are implicated in ciliary motilities across protists and mammals. How they function and whether they act redundantly, however, remain unclear. Here, we show that they play distinct roles in mammals. Kif6 forms puncta that move bidirectionally without or with IFT-B particles along axonemes, whereas Kif9 is immobilized on ciliary central apparatus. Only Kif6 binds to and glides microtubules, and the activities are self-inhibited. Kif6 deficiency in mice impairs directional ciliary beat across ependymal tissues and cerebrospinal fluid flow, resulting in severe hydrocephalus and high mortality, whereas Kif9 deficiency induces mild hydrocephalus without obviously defective ciliary beat and life span. Both Kif6-/- and Kif9-/- males are infertile but show respectively oligozoospermia with poor sperm motility and defective forward motion of sperms. These results suggest Kif6 as a motile cilia-specific IFT motor and Kif9 as a central apparatus regulator.

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Fang, C., Pan, X., Li, D., Chen, Y., Li, L., Gao, Q., Zhu, X., Yan, X.. 2023-11-09. Distinct functions of the kinesin-9 family in mammalian motile cilia. https://doi.org/10.1101/2023.11.09.564704

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