CFAP53 regulates mammalian cilia-type motility patterns through differential localization and recruitment of axonemal dynein components.

CFAP53 regulates mammalian cilia-type motility patterns through differential localization and recruitment of axonemal dynein components.
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DOI:
10.1371/journal.pgen.1009232
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发表时间:
2020-12
期刊:
影响因子:
4.5
通讯作者:
Hamada H
Hamada H
中科院分区:
生物学2区
文献类型:
--
作者:
Ide T;Twan WK;Lu H;Ikawa Y;Lim LX;Henninger N;Nishimura H;Takaoka K;Narasimhan V;Yan X;Shiratori H;Roy S;Hamada H

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运动纤毛可以以不同的模式跳动,但运动性的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CFAP 53在小鼠不同纤毛类型的运动中的作用。虽然Cfap 53突变体的结(9+0)纤毛是不动的,但气管和室管膜(9+2)纤毛保留运动性,尽管具有改变的搏动模式。在节纤毛中,CFAP 53主要定位于基部(中心粒卫星),而在气管纤毛中,CFAP 53也沿着整个轴丝存在。CFAP 53与微管紧密结合,并与轴丝动力蛋白和动力蛋白对接复合物组分TTC 25相互作用。TTC 25和外动力蛋白臂(ODA)从结纤毛中丢失,但在Cfap 53-/-小鼠的气管纤毛中大部分保持。因此,CFAP 53在结纤毛的基础上促进TTC 25和动力蛋白的轴丝运输,而9+2纤毛中的轴丝CFAP 53稳定动力蛋白与微管的结合。我们的研究确定了CFAP 53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。运动纤毛在各种组织和细胞类型中驱动上皮细胞上的流体流动或促进细胞运动。有两种类型的运动纤毛。在气管上皮细胞和脑室管膜细胞上发现了具有9+2微管构型的运动纤毛,并且在有效和恢复性中风中表现出平面搏动。另一方面,在胚胎结中发现9+0运动纤毛,显示旋转运动,并参与建立内脏器官的左右不对称。然而,这是不是很好地理解这两种类型的运动纤毛表现出其特有的运动模式。我们已经揭示了CFAP 53蛋白在小鼠9+0与9+2运动纤毛中的不同作用和亚细胞定位。我们的数据提供了新的见解运动差异的分子基础,这两种类型的哺乳动物能动纤毛的特点。
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. Motile cilia in various kinds of tissues and cell-types drive fluid flow over epithelia or facilitate cellular locomotion. There are two types of motile cilia. Motile cilia with a 9+2 configuration of microtubules are found on tracheal epithelial cells and brain ependymal cells, and exhibit planar beating with effective and recovery strokes. On the other hand, 9+0 motile cilia are found in the embryonic node, show rotational movement and are involved in establishing left-right asymmetry of visceral organs. However, it is not well understood how these two types of motile cilia exhibit their characteristic motion patterns. We have uncovered distinct roles and subcellular localization of the CFAP53 protein in 9+0 versus the 9+2 motile cilia of the mouse. Our data provide novel insights into the molecular basis of motility differences that characterize these two types of mammalian motile cilia.
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