Laboratory for Organismal Patterning, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan.
Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan.
PLoS Genet. 2020 Dec 21;16(12):e1009232. doi: 10.1371/journal.pgen.1009232. eCollection 2020 Dec.
Motile cilia can beat with distinct patterns, but how motility variations are regulated remain obscure. Here, we have studied the role of the coiled-coil protein CFAP53 in the motility of different cilia-types in the mouse. While node (9+0) cilia of Cfap53 mutants were immotile, tracheal and ependymal (9+2) cilia retained motility, albeit with an altered beat pattern. In node cilia, CFAP53 mainly localized at the base (centriolar satellites), whereas it was also present along the entire axoneme in tracheal cilia. CFAP53 associated tightly with microtubules and interacted with axonemal dyneins and TTC25, a dynein docking complex component. TTC25 and outer dynein arms (ODAs) were lost from node cilia, but were largely maintained in tracheal cilia of Cfap53-/- mice. Thus, CFAP53 at the base of node cilia facilitates axonemal transport of TTC25 and dyneins, while axonemal CFAP53 in 9+2 cilia stabilizes dynein binding to microtubules. Our study establishes how differential localization and function of CFAP53 contributes to the unique motion patterns of two important mammalian cilia-types.
纤毛可以以不同的模式进行摆动，但运动变化是如何调节的仍然不清楚。在这里，我们研究了卷曲螺旋蛋白 CFAP53 在不同类型的小鼠纤毛运动中的作用。虽然 Cfap53 突变体的节点（9+0）纤毛不能运动，但气管和室管膜（9+2）纤毛仍然保持运动，尽管摆动模式发生了改变。在节点纤毛中，CFAP53 主要定位于基底（中心粒卫星），而在气管纤毛中，它也存在于整个轴丝上。CFAP53 与微管紧密结合，并与轴丝动力蛋白和 TTC25 相互作用，TTC25 是动力蛋白 docking 复合物的一个组成部分。节点纤毛中的 TTC25 和外动力蛋白臂（ODAs）丢失，但 Cfap53-/- 小鼠的气管纤毛中则大量存在。因此，位于节点纤毛基底的 CFAP53 促进了 TTC25 和动力蛋白的轴丝运输，而 9+2 纤毛中的轴丝 CFAP53 稳定了动力蛋白与微管的结合。我们的研究建立了 CFAP53 的差异定位和功能如何有助于两种重要的哺乳动物纤毛类型的独特运动模式。
