A key regulatory protein for flagellum length control in stable flagella

A key regulatory protein for flagellum length control in stable flagella
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稳定鞭毛中鞭毛长度控制的关键调节蛋白

DOI:
10.1101/872952
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发表时间:
2019
期刊:
--
影响因子:
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通讯作者:
Atkins M
Atkins M
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作者:
Atkins M

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纤毛和鞭毛是高度保守的微管细胞器,在细胞运动和感知中起重要作用。它们可以是高度动态的,寿命很短,如初级纤毛、腺体腺体;也可以是非常稳定的,寿命很长,如精子中的光感受器或许多原生细胞的鞭毛[,]。虽然细胞类型之间的长度有很大的差异,但对于给定的细胞类型,通常有一个定义的长度。许多单细胞鞭毛和纤毛生物有一个额外的挑战,因为它们必须保持鞭毛/纤毛在规定的长度,同时在同一个细胞中生长新的鞭毛/纤毛。目前尚不清楚这是如何实现的。提出了一种维持稳定鞭毛的生长-锁定模型,其中分子锁用于防止鞭毛组装后长度的变化。这种锁如何运作的分子机制尚不清楚,但在必须维持现有鞭毛而新鞭毛组装的细胞中可能很重要。本研究表明,Cep164C参与了布鲁氏瘤内鞭毛基部的锁定机制。它只定位于完全组装的鞭毛的基体的过渡纤维上,在组装的鞭毛上缺失。事实上,基底体在锥虫体内组装后的第三个细胞周期才获得Cep164C。耗竭导致鞭毛生长失调,鞭毛变长或变短;与鞭毛锁定机制的缺陷相符。通过控制成分进入旧的组装鞭毛,可以维持稳定的鞭毛,但限制了进一步的生长。这为许多真核单细胞在分裂前维持现有鞭毛同时生长新鞭毛提供了重要的解释。这项工作还揭示了Cep164在真核生物中的其他调节作用。
Cilia and flagella are highly conserved microtubule-based organelles that have important roles in cell motility and sensing . They can be highly dynamic and short lived such as primary cilia orChlamydomonasor very stable and long lived such as those in spermatozoa photoreceptors or the flagella of many protist cells [,]. Although there is a wide variation in length between cell types, there is generally a defined length for a given cell type . Many unicellular flagellated and ciliated organisms have an additional challenge as they must maintain flagella/cilia at a defined length whilst also growing new flagella/cilia in the same cell. It is not currently understood how this is achieved. A grow-and-lock model was proposed for the maintenance of stable flagella where a molecular lock is applied to prevent flagellum length change after assembly . The molecular mechanisms of how this lock operates are unknown, but could be important in cells where an existing flagellum must be maintained whilst a new flagellum assembles. Here we show that Cep164C contributes to the locking mechanism at the base of the flagellum inTrypanosoma brucei. It is only localised on the transition fibres of basal bodies of fully assembled flagella and missing from assembling flagella. In fact, basal bodies only acquire Cep164C in the third cell cycle after they assemble in trypanosomes. Depletion leads to dysregulation of flagellum growth with both longer and shorter flagella; consistent with defects in a flagellum locking mechanism. By controlling delivery of components into the old assembled flagellum, maintenance of stable flagella can occur but limits further growth. This offers an important explanation for how many eukaryotic unicellular cells maintain their existing flagella whilst growing new ones before these cells divide. This work also reveals additional regulatory roles for Cep164 in eukaryotic organisms.
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