Wdr47, Camsaps, and Katanin cooperate to generate ciliary central microtubules.

Wdr47, Camsaps, and Katanin cooperate to generate ciliary central microtubules.
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Wdr47、Camsaps 和 Katanin 合作生成睫状中央微管

DOI:
10.1038/s41467-021-26058-5
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发表时间:
2021-10-04
影响因子:
16.6
通讯作者:
Yan X
Yan X
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Liu H;Zheng J;Zhu L;Xie L;Chen Y;Zhang Y;Zhang W;Yin Y;Peng C;Zhou J;Zhu X;Yan X

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轴突中央对(CP)是非中心体微管,对平面纤毛跳动至关重要。然而,人们对它们是如何形成的却知之甚少。在这里,我们发现哺乳动物CP的形成需要Wdr47、Camsaps和Katanin的微管切断活性。卡他蛋白切断外周微管在新生纤毛中产生中心微管种子。Camsaps稳定种子的负端,促进微管的生长,而Wdr47将Camsaps集中在轴突中央管腔中,以适当地定位中央微管。小鼠多纤毛wdr47缺乏导致CP完全丧失、旋转搏动和原发性纤毛运动障碍。Camsaps或其微管结合区过表达可诱导wdr47−/−室管膜细胞的中心微管,但其代价是效率低、数量异常和位置错误。Katanin的水平和活动也会影响中央微管的数量。我们提出Wdr47、Camsaps和Katanin共同作用,在极化亚细胞区室中产生非中心体微管阵列。
The axonemal central pair (CP) are non-centrosomal microtubules critical for planar ciliary beat. How they form, however, is poorly understood. Here, we show that mammalian CP formation requires Wdr47, Camsaps, and microtubule-severing activity of Katanin. Katanin severs peripheral microtubules to produce central microtubule seeds in nascent cilia. Camsaps stabilize minus ends of the seeds to facilitate microtubule outgrowth, whereas Wdr47 concentrates Camsaps into the axonemal central lumen to properly position central microtubules.Wdr47deficiency in mouse multicilia results in complete loss of CP, rotatory beat, and primary ciliary dyskinesia. Overexpression of Camsaps or their microtubule-binding regions induces central microtubules inWdr47−/−ependymal cells but at the expense of low efficiency, abnormal numbers, and wrong location. Katanin levels and activity also impact the central microtubule number. We propose that Wdr47, Camsaps, and Katanin function together for the generation of non-centrosomal microtubule arrays in polarized subcellular compartments.
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