Modes of flagellar assembly in Chlamydomonas reinhardtii and Trypanosoma brucei.
Modes of flagellar assembly in Chlamydomonas reinhardtii and Trypanosoma brucei.
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作者：
Höög JL;Lacomble S;O'Toole ET;Hoenger A;McIntosh JR;Gull K
鞭毛生长缺陷与许多人类疾病有关。鞭毛生长的核心是微管的组织，微管从基体聚合形成轴丝，轴丝由数百种蛋白质组成。鞭毛存在于所有真核生物门中，但鞭毛生长的机制以及该过程在进化中的保守性均未知。在这里，我们使用（冷冻）电子断层扫描研究蛋白质复合物如何组装到生长的轴丝尖端上。在莱茵衣藻中同时添加微管和相关蛋白质。然而，在布氏锥虫中，通过随后添加预先形成的蛋白质复合物，杂乱的微管阵列被排列成轴丝结构。组装后，T. brucei 过渡区改变了结构，并且其与中心对的关联松弛。我们的结论是，形成鞭毛的方法有多种，并且在评估鞭毛缺陷之前，物种特异性的结构知识至关重要。 DOI：http://dx.doi.org/10.7554/eLife.01479.001 有些细胞有一个鞭状的附属物，称为鞭毛。它最常用于推动细胞，特别是在精子细胞中，但它也可以参与感知周围环境的线索。鞭毛存在于生命的所有三个领域——真核生物（包括动物）、细菌和称为古细菌的古代单细胞生物——并且它们在每个领域中执行相似的功能。然而，它们在蛋白质组成、整体结构和推进机制方面也存在显着差异。真核生物鞭毛的核心由 20 根称为“微管”的中空细丝组成，这些细丝排列成九对微管，围绕两个中央微管形成一个环。核心还含有许多其他蛋白质，但尚不清楚所有这些成分如何聚集在一起形成工作鞭毛。此外，尚不清楚不同真核生物类群的鞭毛是否都以相同的方式组装。现在，Höög 等人。研究发现，虽然真核生物鞭毛的核心结构高度保守，但它可以以明显不同的方式组装。某些真核生物物种——例如莱茵衣藻（一种单细胞绿藻）和布氏锥虫（导致非洲昏睡病的原生寄生虫）——在细胞分裂时必须长出新的鞭毛，以便每个新细胞都能游泳。 Höög 等人使用一种称为电子断层扫描的电子显微镜。可以在三个维度上看到生长的鞭毛的详细结构。起初，这两个远缘物种的鞭毛核心以相同的方式生长。然而，随着鞭毛变长，它们的核心以完全不同的方式生长。较长鞭毛中的微管丝在藻类中以同步方式生长，但在原生生物中以无序的方式生长。 Höög 等人的结果。说明根据少数模式物种的研究得出概括性结论是不可取的。然而，由于已知鞭毛缺陷会导致人类多种疾病，这一知识可能会为未来旨在开发治疗不孕症、呼吸系统问题和某些癌症的方法的研究提供信息。 DOI：http://dx.doi.org/10.7554/eLife.01479.002
Defects in flagella growth are related to a number of human diseases. Central to flagellar growth is the organization of microtubules that polymerize from basal bodies to form the axoneme, which consists of hundreds of proteins. Flagella exist in all eukaryotic phyla, but neither the mechanism by which flagella grow nor the conservation of this process in evolution are known. Here, we study how protein complexes assemble onto the growing axoneme tip using (cryo) electron tomography. In Chlamydomonas reinhardtii microtubules and associated proteins are added simultaneously. However, in Trypanosoma brucei, disorganized arrays of microtubules are arranged into the axoneme structure by the later addition of preformed protein complexes. Post assembly, the T. brucei transition zone alters structure and its association with the central pair loosens. We conclude that there are multiple ways to form a flagellum and that species-specific structural knowledge is critical before evaluating flagellar defects. DOI: http://dx.doi.org/10.7554/eLife.01479.001 Some cells have a whip-like appendage called a flagellum. This is most often used to propel the cell, notably in sperm cells, but it can also be involved in sensing cues in the surrounding environment. Flagella are found in all three domains of life—the eukaryotes (which include the animals), bacteria and ancient, single-celled organisms called Archaea—and they perform similar functions in each domain. However, they also differ significantly in their protein composition, overall structure, and mechanism of propulsion. The core of the flagellum in eukaryotes is made up of 20 hollow filaments called ‘microtubules’ arranged so that nine pairs of microtubules form a ring around two central microtubules. The core also contains many other proteins, but it is not clear how all these components come together to make a working flagellum. Moreover, it is not known if the flagella of different groups of eukaryotes are all assembled in the same way. Now, Höög et al. have discovered that although the core structure of the eukaryote flagellum is highly conserved, it can be assembled in markedly different ways. Some species of eukaryote—such as Chlamydomonas reinhardtii, a single-celled green alga, and Trypanosoma brucei, the protist parasite that causes African sleeping sickness—must grow new flagella when their cells divide, so that each new cell can swim. Using a form of electron microscopy called electron tomography, Höög et al. could see the detailed structure of the growing flagella in three dimensions. At first the cores of the flagella in these two distantly related species grow in the same way. However as the flagella get longer their cores grow in completely different ways. The microtubule filaments in longer flagella grow in a synchronized manner in the alga, but in a disorganized way in the protist. The results of Höög et al. illustrate that it is not advisable to draw generalised conclusions based on studies of a few model species. However, since defects in flagella are known to cause several diseases in humans, this knowledge might inform future studies aimed at developing treatments for infertility, respiratory problems, and certain kinds of cancer. DOI: http://dx.doi.org/10.7554/eLife.01479.002