In situ ultrastructures of two evolutionarily distant apicomplexan rhoptry secretion systems.

In situ ultrastructures of two evolutionarily distant apicomplexan rhoptry secretion systems.
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两种进化远处的Apicomplexan Rhoptry分泌系统的原位超微结构。

DOI:
10.1038/s41467-021-25309-9
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发表时间:
2021-08-17
影响因子:
16.6
通讯作者:
Chang YW
Chang YW
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Mageswaran SK;Guérin A;Theveny LM;Chen WD;Martinez M;Lebrun M;Striepen B;Chang YW

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顶复门的寄生虫引起重要的疾病,包括疟疾、隐孢子虫病和弓形虫病。这些细胞内病原体将一种基本细胞器(棒状体)的内容物注入宿主细胞,以促进入侵和感染。然而,这种真核分泌系统的结构和机制仍然是难以捉摸的。在这里,使用冷冻电子断层扫描和subtomogram平均,我们报告的保守架构的棒状分泌系统在两个进化上遥远的apicomplexans,隐孢子虫和弓形虫的入侵阶段。在这两个物种中,我们确定螺旋丝,这似乎是形状和划分的棒状体,和顶端囊泡(AV),这有利于对接的棒状体尖端在寄生虫的顶端区域的帮助下,一个精心设计的超微结构命名的棒状体分泌器(RSA); RSA锚定AV在寄生虫质膜。T的消失。刚地Nd 9是棒状体分泌所需的蛋白质,其破坏RSA超微结构和AV锚定。此外,T.弓形虫含有一排AV样囊泡,其与一对微管相互作用并向AV聚集,从而导致AV重新加载和释放多个棒状体的工作模型。总之,我们的分析提供了一个超微结构框架,以了解这些重要的寄生虫如何将效应子传递到宿主细胞中。棒状体是顶复门寄生虫的顶端分泌细胞器,对宿主细胞的侵入至关重要。在这里,Mageswaran等人提供了来自两种病原体的棒状体的原位超微结构,揭示了保守的结构,包括腔丝和独特的对接机制。
Parasites of the phylum Apicomplexa cause important diseases including malaria, cryptosporidiosis and toxoplasmosis. These intracellular pathogens inject the contents of an essential organelle, the rhoptry, into host cells to facilitate invasion and infection. However, the structure and mechanism of this eukaryotic secretion system remain elusive. Here, using cryo-electron tomography and subtomogram averaging, we report the conserved architecture of the rhoptry secretion system in the invasive stages of two evolutionarily distant apicomplexans, Cryptosporidium parvum and Toxoplasma gondii. In both species, we identify helical filaments, which appear to shape and compartmentalize the rhoptries, and an apical vesicle (AV), which facilitates docking of the rhoptry tip at the parasite’s apical region with the help of an elaborate ultrastructure named the rhoptry secretory apparatus (RSA); the RSA anchors the AV at the parasite plasma membrane. Depletion of T. gondii Nd9, a protein required for rhoptry secretion, disrupts the RSA ultrastructure and AV-anchoring. Moreover, T. gondii contains a line of AV-like vesicles, which interact with a pair of microtubules and accumulate towards the AV, leading to a working model for AV-reloading and discharging of multiple rhoptries. Together, our analyses provide an ultrastructural framework to understand how these important parasites deliver effectors into host cells. The rhoptry is an apical secretory organelle of apicomplexan parasites that is essential for host cell invasion. Here, Mageswaran et al. provide in situ ultrastructures of rhoptries from two pathogens, revealing a conserved architecture including luminal filaments and a distinct docking mechanism.
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