Kif6和Kif9在哺乳动物纤毛运输和运动中的不同作用

IF 7.4 1区 生物学 Q1 CELL BIOLOGY Journal of Cell Biology Pub Date : 2024-11-04 Epub Date: 2024-08-19 DOI:10.1083/jcb.202312060
Chuyu Fang, Xinwen Pan, Di Li, Wei Chen, Ying Huang, Yawen Chen, Luan Li, Qi Gao, Xin Liang, Dong Li, Xueliang Zhu, Xiumin Yan
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引用次数: 0

摘要

纤毛搏动和纤毛内运输依赖于动力蛋白和驱动蛋白马达。驱动蛋白-9 家族成员 Kif6 和 Kif9 与原生动物和哺乳动物的纤毛运动有关。然而,它们是如何起作用的以及它们是否起冗余作用仍不清楚。在这里,我们发现 Kif6 和 Kif9 在哺乳动物中发挥着不同的作用。Kif6 形成的点沿着轴丝双向移动,而 Kif9 似乎在纤毛中心器上的区域内摆动。一致的是,只有 Kif6 在体外显示出基于微管的运动活性,其纤毛定位需要其 ATPase 活性。小鼠缺乏 Kif6 会破坏上皮组织中协调的睫状肌搏动,并损害脑脊液流动,导致严重脑积水和高死亡率。Kif9 缺乏会导致轻度脑积水,但不会明显影响睫状肌搏动或寿命。Kif6-/- 和 Kif9-/- 雄性不育,但分别表现出精子活力差和精子前向运动缺陷的少精子症。这些结果表明 Kif6 是货物运输的马达,而 Kif9 则是中央装置的调节器。
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Distinct roles of Kif6 and Kif9 in mammalian ciliary trafficking and motility.

Ciliary beat and intraflagellar transport depend on dynein and kinesin motors. The kinesin-9 family members Kif6 and Kif9 are implicated in motile cilia motilities across protists and mammals. How they function and whether they act redundantly, however, remain unclear. Here, we show that Kif6 and Kif9 play distinct roles in mammals. Kif6 forms puncta that move bidirectionally along axonemes, whereas Kif9 appears to oscillate regionally on the ciliary central apparatus. Consistently, only Kif6 displays microtubule-based motor activity in vitro, and its ciliary localization requires its ATPase activity. Kif6 deficiency in mice disrupts coordinated ciliary beat across ependymal tissues and impairs cerebrospinal fluid flow, resulting in severe hydrocephalus and high mortality. Kif9 deficiency causes mild hydrocephalus without obviously affecting the ciliary beat or the lifespan. Kif6-/- and Kif9-/- males are infertile but exhibit oligozoospermia with poor sperm motility and defective forward motion of sperms, respectively. These results suggest Kif6 as a motor for cargo transport and Kif9 as a central apparatus regulator.

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来源期刊
Journal of Cell Biology
Journal of Cell Biology 生物-细胞生物学
CiteScore
12.60
自引率
2.60%
发文量
213
审稿时长
1 months
期刊介绍: The Journal of Cell Biology (JCB) is a comprehensive journal dedicated to publishing original discoveries across all realms of cell biology. We invite papers presenting novel cellular or molecular advancements in various domains of basic cell biology, along with applied cell biology research in diverse systems such as immunology, neurobiology, metabolism, virology, developmental biology, and plant biology. We enthusiastically welcome submissions showcasing significant findings of interest to cell biologists, irrespective of the experimental approach.
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