Nature Communications ( IF 14.7 ) Pub Date : 2024-01-08 , DOI: 10.1038/s41467-023-44577-1 Xueming Meng 1 , Cong Xu 1 , Jiawei Li 1 , Benhua Qiu 2 , Jiajun Luo 2 , Qin Hong 1 , Yujie Tong 1 , Chuyu Fang 2 , Yanyan Feng 3 , Rui Ma 4 , Xiangyi Shi 4 , Cheng Lin 1 , Chen Pan 5 , Xueliang Zhu 2, 6 , Xiumin Yan 3 , Yao Cong 1, 6
Radial spokes (RS) transmit mechanochemical signals between the central pair (CP) and axonemal dynein arms to coordinate ciliary motility. Atomic-resolution structures of metazoan RS and structures of axonemal complexes in ependymal cilia, whose rhythmic beating drives the circulation of cerebrospinal fluid, however, remain obscure. Here, we present near-atomic resolution cryo-EM structures of mouse RS head-neck complex in both monomer and dimer forms and reveal the intrinsic flexibility of the dimer. We also map the genetic mutations related to primary ciliary dyskinesia and asthenospermia on the head-neck complex. Moreover, we present the cryo-ET and sub-tomogram averaging map of mouse ependymal cilia and build the models for RS1-3, IDAs, and N-DRC. Contrary to the conserved RS structure, our cryo-ET map reveals the lack of IDA-b/c/e and the absence of Tektin filaments within the A-tubule of doublet microtubules in ependymal cilia compared with mammalian respiratory cilia and sperm flagella, further exemplifying the structural diversity of mammalian motile cilia. Our findings shed light on the stepwise mammalian RS assembly mechanism, the coordinated rigid and elastic RS-CP interaction modes beneficial for the regulation of asymmetric ciliary beating, and also facilitate understanding on the etiology of ciliary dyskinesia-related ciliopathies and on the ependymal cilia in the development of hydrocephalus.
中文翻译:
哺乳动物径向辐条的多尺度结构和室管膜纤毛轴丝复合体的分歧
径向辐条(RS)在中央对(CP)和轴丝动力蛋白臂之间传输机械化学信号,以协调纤毛运动。然而,后生动物 RS 的原子分辨率结构和室管膜纤毛中轴丝复合体的结构仍然不清楚,室管膜纤毛的节律性跳动驱动脑脊液的循环。在这里,我们展示了小鼠 RS 头颈复合物单体和二聚体形式的近原子分辨率冷冻电镜结构,并揭示了二聚体的内在灵活性。我们还在头颈复合体上绘制了与原发性纤毛运动障碍和弱精子症相关的基因突变图。此外,我们还展示了小鼠室管膜纤毛的冷冻 ET 和亚断层扫描平均图,并建立了 RS1-3、IDAs 和 N-DRC 模型。与保守的 RS 结构相反,我们的冷冻 ET 图显示,与哺乳动物呼吸道纤毛和精子鞭毛相比,室管膜纤毛双联微管 A 管内缺乏 IDA-b/c/e 和 Tektin 丝,进一步例证了哺乳动物运动纤毛的结构多样性。我们的研究结果揭示了逐步哺乳动物 RS 组装机制、有利于调节不对称纤毛跳动的协调刚性和弹性 RS-CP 相互作用模式,并有助于了解纤毛运动障碍相关纤毛病的病因和室管膜纤毛脑积水的发展。