Vertebrate Dynein-f depends on Wdr78 for axonemal localization and is essential for ciliary beat.

Vertebrate Dynein-f depends on Wdr78 for axonemal localization and is essential for ciliary beat.
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脊椎动物 Dynein-f 依赖于 Wdr78 进行轴丝定位,对于纤毛跳动至关重要

DOI:
10.1093/jmcb/mjy043
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发表时间:
2019-05-01
影响因子:
5.5
通讯作者:
Zhu X
Zhu X
中科院分区:
生物学1区
文献类型:
--
作者:
Zhang Y;Chen Y;Zheng J;Wang J;Duan S;Zhang W;Yan X;Zhu X

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运动纤毛和鞭毛是基于微管的细胞器,对细胞运动和细胞外液通过跳动流动很重要。虽然在单细胞衣原体中已经广泛研究了驱动纤毛搏动的轴突动力蛋白,但是这些知识在多大程度上可以应用于脊椎动物还知之甚少。在衣原体中,动力蛋白-f控制鞭毛波形,但不控制搏动。其重链(HC)的鞭毛组装需要其中间链(IC)IC 140,但不需要IC 138。在这里,我们表明,不像它的衣原体对应物,脊椎动物Dynein-f是必不可少的纤毛节拍。我们证实Wdr 78是IC 138的脊椎动物直向同源物。Wdr 78与动力蛋白-f亚基如Dnah 2(a HC)和Wdr 63(IC 140直向同源物)相关。在哺乳动物细胞中表达为运动纤毛特异性蛋白。通过RNAi消耗Wdr 78或Dnah 2使小鼠室管膜纤毛瘫痪。斑马鱼Wdr 78 morphants显示纤毛病相关的表型,如弯曲的身体,脑积水,异常耳石,随机左右不对称,和前肾囊肿,伴随着麻痹的前肾纤毛。此外,动力蛋白-f的所有HC和IC未能定位在Wdr 78耗尽的小鼠室管膜纤毛中。因此,动力蛋白-f的功能和亚基依赖性在进化中改变,可能是为了符合高等生物中纤毛的作用。
Motile cilia and flagella are microtubule-based organelles important for cell locomotion and extracellular liquid flow through beating. Although axonenal dyneins that drive ciliary beat have been extensively studied in unicellular Chlamydomonas, to what extent such knowledge can be applied to vertebrate is poorly known. In Chlamydomonas, Dynein-f controls flagellar waveforms but is dispensable for beating. The flagellar assembly of its heavy chains (HCs) requires its intermediate chain (IC) IC140 but not IC138. Here we show that, unlike its Chlamydomonas counterpart, vertebrate Dynein-f is essential for ciliary beat. We confirmed that Wdr78 is the vertebrate orthologue of IC138. Wdr78 associated with Dynein-f subunits such as Dnah2 (a HC) and Wdr63 (IC140 orthologue). It was expressed as a motile cilium-specific protein in mammalian cells. Depletion of Wdr78 or Dnah2 by RNAi paralyzed mouse ependymal cilia. Zebrafish Wdr78 morphants displayed ciliopathy-related phenotypes, such as curved bodies, hydrocephalus, abnormal otolith, randomized left–right asymmetry, and pronephric cysts, accompanied with paralyzed pronephric cilia. Furthermore, all the HCs and ICs of Dynein-f failed to localize in the Wdr78-depleted mouse ependymal cilia. Therefore, both the functions and subunit dependency of Dynein-f are altered in evolution, probably to comply with ciliary roles in higher organisms.
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在衣原体中,内臂组件和鞭毛运动所需的1α动力蛋白重链中的域。
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