An Alveolata secretory machinery adapted to parasite host cell invasion.

An Alveolata secretory machinery adapted to parasite host cell invasion.
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DOI:
10.1038/s41564-020-00854-z
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发表时间:
2021-04
影响因子:
28.3
通讯作者:
Lebrun M
Lebrun M
中科院分区:
生物学1区
文献类型:
--
作者:
Aquilini E;Cova MM;Mageswaran SK;Dos Santos Pacheco N;Sparvoli D;Penarete-Vargas DM;Najm R;Graindorge A;Suarez C;Maynadier M;Berry-Sterkers L;Urbach S;Fahy PR;Guérin AN;Striepen B;Dubremetz JF;Chang YW;Turkewitz AP;Lebrun M

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顶复门是单细胞真核生物和专性细胞内寄生虫,包括疟疾的病原体疟原虫和最广泛的人畜共患病原体之一弓形虫。它们具有专门的分泌细胞器,棒状体,在入侵过程中进行调节胞吐。棒状体蛋白被直接注射到宿主细胞中以支持入侵和破坏宿主免疫功能。它们被释放的机制尚不清楚,似乎与细菌、酵母、动物或植物中的机制不同。在这里,我们表明,棒状分泌Apicomplexa股结构和遗传因素的纤毛,他们的自由生活的亲戚外泌机械。棒状体的胞吐作用依赖于镶嵌在寄生虫顶端质膜上的玫瑰花结状膜内颗粒。形成这个玫瑰花结需要多个非放电(Nd)蛋白保守和限制纤毛虫,腰鞭毛虫,顶复门,共同构成的超门Alveolata。我们确定了Nd6与顶囊泡在网站的胞吐。夹在莲座丛和棒状体的顶端之间,这个小泡作为棒状体分泌机器的中心元件出现。我们的研究结果描述了一个保守的分泌系统,适用于提供防御自由生活的单细胞真核生物和宿主细胞注射在细胞内寄生虫。
Apicomplexa are unicellular eukaryotes and obligate intracellular parasites, including Plasmodium, the causative agent of malaria and Toxoplasma, one of the most widespread zoonotic pathogens. They possess specialized secretory organelles, the rhoptries, that undergo regulated exocytosis during invasion. Rhoptry proteins are injected directly into the host cell to support invasion and subversion of host immune function. The mechanism by which they are discharged is unclear and appears distinct from those in bacteria, yeast, animals or plants. Here we show that rhoptry secretion in Apicomplexa shares structural and genetic elements with the exocytic machinery of ciliates, their free-living relatives. Rhoptry exocytosis depends on intramembranous particles in the shape of a rosette embedded into the plasma membrane of the parasite apex. Formation of this rosette requires multiple Non-discharge (Nd) proteins conserved and restricted to ciliates, dinoflagellates, and Apicomplexa, that together constitute the superphylum Alveolata. We identified Nd6 in association with an apical vesicle at the site of exocytosis. Sandwiched between the rosette and the tip of the rhoptry, this vesicle appears as a central element of the rhoptry secretion machine. Our results describe a conserved secretion system that was adapted to provide defense for free-living unicellular eukaryotes and host cell injection in intracellular parasites.
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