Dawe Helen R, Shaw Michael K, Farr Helen, Gull Keith
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
BMC Biol. 2007 Aug 7;5:33. doi: 10.1186/1741-7007-5-33.
Impairment of cilia and flagella function underlies a growing number of human genetic diseases. Mutations in hydin in hy3 mice cause lethal communicating hydrocephalus with early onset. Hydin was recently identified as an axonemal protein; however, its function is as yet unknown.
Here we use RNAi in Trypanosoma brucei to address this issue and demonstrate that loss of Hydin causes slow growth and a loss of cell motility. We show that two separate defects in newly-formed flagellar central pair microtubules underlie the loss of cell motility. At early time-points after RNAi induction, the central pair becomes mispositioned, while at later time points the central pair is lost. While the basal body is unaffected, both defects originate at the basal plate, reflecting a role for TbHydin throughout the length of the central pair.
Our data provide the first evidence of Hydin's role within the trypanosome axoneme, and reveal central pair anomalies and thus impairment of ependymal ciliary motility as the likely cause of the hydrocephalus observed in the hy3 mouse.
纤毛和鞭毛功能受损是越来越多人类遗传疾病的基础。hy3小鼠中hydin基因的突变会导致早发性致死性交通性脑积水。Hydin最近被鉴定为一种轴丝蛋白；然而，其功能尚不清楚。
在这里，我们利用布氏锥虫中的RNA干扰来解决这个问题，并证明Hydin的缺失会导致生长缓慢和细胞运动能力丧失。我们表明，新形成的鞭毛中央微管中的两个独立缺陷是细胞运动能力丧失的基础。在RNA干扰诱导后的早期时间点，中央微管位置发生错误，而在后期时间点，中央微管消失。虽然基体未受影响，但这两个缺陷都起源于基底板，反映了TbHydin在中央微管全长中的作用。
我们的数据首次证明了Hydin在锥虫轴丝中的作用，并揭示了中央微管异常以及由此导致的室管膜纤毛运动受损是hy3小鼠中观察到的脑积水的可能原因。
Zotero 插件
