Zhao Lijuan, Xie Haibo, Kang Yunsi, Lin Yiwen, Liu Gai, Sakato-Antoku Miho, Patel-King Ramila S, Wang Bing, Wan Cuihong, King Stephen M, Zhao Chengtian, Huang Kaiyao
Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, 430072 Wuhan, China.
College of Life Sciences, University of Chinese Academy of Sciences, 100039 Beijing, China.
Proc Natl Acad Sci U S A. 2021 Apr 27;118(17). doi: 10.1073/pnas.2015689118.
Coordinated beating is crucial for the function of multiple cilia. However, the molecular mechanism is poorly understood. Here, we characterize a conserved ciliary protein CYB5D1 with a heme-binding domain and a cordon-bleu ubiquitin-like domain. Mutation or knockdown of in zebrafish impaired coordinated ciliary beating in the otic vesicle and olfactory epithelium. Similarly, the two flagella of an insertional mutant of the CYB5D1 ortholog in () showed an uncoordinated pattern due to a defect in the -flagellum. Biochemical analyses revealed that CrCYB5D1 is a radial spoke stalk protein that binds heme only under oxidizing conditions. Lack of CrCYB5D1 resulted in a reductive shift in flagellar redox state and slowing down of the phototactic response. Treatment of with oxidants restored coordinated flagellar beating. Taken together, these data suggest that CrCYB5D1 may integrate environmental and intraciliary signals and regulate the redox state of cilia, which is crucial for the coordinated beating of multiple cilia.
协调摆动对于多个纤毛的功能至关重要。然而，其分子机制尚不清楚。在这里，我们鉴定了一种保守的纤毛蛋白CYB5D1，它具有一个血红素结合结构域和一个类泛素蓝带结构域。斑马鱼中CYB5D1的突变或敲低会损害耳泡和嗅觉上皮中纤毛的协调摆动。同样，衣藻中CYB5D1直系同源基因插入突变体的两条鞭毛由于鞭毛存在缺陷而呈现不协调模式。生化分析表明，CrCYB5D1是一种径向辐条柄蛋白，仅在氧化条件下结合血红素。缺乏CrCYB5D1会导致鞭毛氧化还原状态发生还原转变，并减缓趋光反应。用氧化剂处理衣藻可恢复鞭毛的协调摆动。综上所述，这些数据表明CrCYB5D1可能整合环境信号和纤毛内信号，并调节纤毛的氧化还原状态，这对于多个纤毛的协调摆动至关重要。
