Wei Ying, Hu Huiqing, Lun Zhao-Rong, Li Ziyin
1] Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, 6431 Fannin Street, MSE R214, Houston, Texas 77030, USA [2] Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, and Key Laboratory of Tropical Diseases and Control of the Ministry of Education, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou 510275, China.
Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, 6431 Fannin Street, MSE R214, Houston, Texas 77030, USA.
Nat Commun. 2014 Jun 3;5:4060. doi: 10.1038/ncomms5060.
Centrin is a conserved component of centrioles in animals and basal bodies in flagellated organisms. It also associates with axonemal inner-arm dyneins and regulates cell motility, but the underlying mechanism remains elusive. In Trypanosoma brucei, three of the five centrins associate with the flagellar basal body, but no centrin has been found to regulate flagellar motility. Here we show that TbCentrin3 is a flagellar protein and knockdown of TbCentrin3 compromises cell motility. Tandem affinity purification followed by mass spectrometry identifies an inner-arm dynein, TbIAD5-1, as the TbCentrin3 partner, and knockdown of TbIAD5-1 causes similar cell motility defect. Further, we demonstrate the interdependence of TbCentrin3 and TbIAD5-1 for maintaining a stable complex in the flagellar axoneme. Together, these results identify the essential role of TbCentrin3 in cell motility by maintaining the stability of an inner-arm dynein in the flagellum, which may be shared by all the centrin-containing flagellated and ciliated organisms.
中心蛋白是动物中心粒和鞭毛生物基体中保守的组成部分。它还与轴丝内臂动力蛋白相关联并调节细胞运动,但潜在机制仍不清楚。在布氏锥虫中,五个中心蛋白中的三个与鞭毛基体相关联,但尚未发现有中心蛋白调节鞭毛运动。在此我们表明,TbCentrin3是一种鞭毛蛋白,敲低TbCentrin3会损害细胞运动。串联亲和纯化后进行质谱分析,鉴定出一种内臂动力蛋白TbIAD5-1作为TbCentrin3的伙伴,敲低TbIAD5-1会导致类似的细胞运动缺陷。此外,我们证明了TbCentrin3和TbIAD5-1在维持鞭毛轴丝中稳定复合物方面的相互依赖性。总之,这些结果确定了TbCentrin3通过维持鞭毛内臂动力蛋白的稳定性在细胞运动中的重要作用,这可能为所有含中心蛋白的鞭毛和纤毛生物所共有。