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Kif9 是一种活跃的驱动蛋白马达,对于纤毛的拍打和运动轴丝的近-远轴模式形成是必需的。

Kif9 is an active kinesin motor required for ciliary beating and proximodistal patterning of motile axonemes.

机构信息

Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.

Department of Pediatrics, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd, The University of Texas at Austin, Dell Medical School, Austin, TX 78712, USA.

出版信息

J Cell Sci. 2023 Mar 1;136(5). doi: 10.1242/jcs.259535. Epub 2022 Jun 22.

DOI:10.1242/jcs.259535
PMID:35531639
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9357393/
Abstract

Most motile cilia have a stereotyped structure of nine microtubule outer doublets and a single central pair of microtubules. The central pair of microtubules are surrounded by a set of proteins, termed the central pair apparatus. A specific kinesin, Klp1 projects from the central pair and contributes to ciliary motility in Chlamydomonas. The vertebrate ortholog, Kif9, is required for beating in mouse sperm flagella, but the mechanism of Kif9/Klp1 function remains poorly defined. Here, using Xenopus epidermal multiciliated cells, we show that Kif9 is necessary for ciliary motility and the proper distal localization of not only central pair proteins, but also radial spokes and dynein arms. In addition, single-molecule assays in vitro reveal that Xenopus Kif9 is a long-range processive motor, although it does not mediate long-range movement in ciliary axonemes in vivo. Together, our data suggest that Kif9 is integral for ciliary beating and is necessary for proper axonemal distal end integrity.

摘要

大多数运动纤毛具有九对外周微管二联体和一个单一的中央微管对的刻板结构。中央微管对被一组称为中央对装置的蛋白质所包围。一种特定的驱动蛋白 Klp1 从中央对中伸出,并有助于衣藻中的纤毛运动。脊椎动物的同源物 Kif9 对于小鼠精子鞭毛的跳动是必需的,但 Kif9/Klp1 功能的机制仍未得到很好的定义。在这里,我们使用非洲爪蟾表皮多纤毛细胞表明,Kif9 对于纤毛运动和不仅中央对蛋白,而且辐条和动力蛋白臂的适当远端定位都是必需的。此外,体外的单分子测定表明,非洲爪蟾 Kif9 是一种长程的进行性马达,尽管它在体内的纤毛轴突中并不介导长程运动。总之,我们的数据表明 Kif9 对于纤毛的跳动是必不可少的,并且对于轴突末端的完整性是必要的。

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本文引用的文献

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Cryo-EM structure of an active central apparatus.冷冻电镜结构的活性中央装置。
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Distinct architecture and composition of mouse axonemal radial spoke head revealed by cryo-EM.冷冻电镜揭示了小鼠轴丝放射辐条头部的独特结构和组成。
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Biallelic mutations of CFAP74 may cause human primary ciliary dyskinesia and MMAF phenotype.CFAP74 的双等位基因突变可能导致人类原发性纤毛运动障碍和 MMAF 表型。
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A nonsense variant in NME5 causes human primary ciliary dyskinesia with radial spoke defects.NME5 中的无意义变异导致具有辐射辐条缺陷的人类原发性纤毛运动障碍。
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FASEB J. 2020 Apr;34(4):5389-5400. doi: 10.1096/fj.201902755R. Epub 2020 Feb 19.
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Microtubule-bundling protein Spef1 enables mammalian ciliary central apparatus formation.微管结合蛋白 Spef1 使哺乳动物纤毛中央器形成。
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