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刚地弓形虫微孔介导胞吞作用,以从宿主细胞区室中选择性回收营养物质。

The Toxoplasma micropore mediates endocytosis for selective nutrient salvage from host cell compartments.

机构信息

National Key Laboratory of Veterinary Public Health Security and School of Veterinary Medicine, China Agricultural University, 100193, Beijing, China.

MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, China.

出版信息

Nat Commun. 2023 Feb 22;14(1):977. doi: 10.1038/s41467-023-36571-4.

Abstract

Apicomplexan parasite growth and replication relies on nutrient acquisition from host cells, in which intracellular multiplication occurs, yet the mechanisms that underlie the nutrient salvage remain elusive. Numerous ultrastructural studies have documented a plasma membrane invagination with a dense neck, termed the micropore, on the surface of intracellular parasites. However, the function of this structure remains unknown. Here we validate the micropore as an essential organelle for endocytosis of nutrients from the host cell cytosol and Golgi in the model apicomplexan Toxoplasma gondii. Detailed analyses demonstrated that Kelch13 is localized at the dense neck of the organelle and functions as a protein hub at the micropore for endocytic uptake. Intriguingly, maximal activity of the micropore requires the ceramide de novo synthesis pathway in the parasite. Thus, this study provides insights into the machinery underlying acquisition of host cell-derived nutrients by apicomplexan parasites that are otherwise sequestered from host cell compartments.

摘要

顶复门寄生虫的生长和复制依赖于从宿主细胞中获取营养物质,在宿主细胞内发生增殖,但其营养物质回收的机制仍不清楚。大量超微结构研究记录了在细胞内寄生虫表面有一个带有浓密颈部的质膜内陷,称为微孔。然而,这个结构的功能仍然未知。在这里,我们验证了微孔是顶复门寄生虫弓形虫从宿主细胞质和高尔基体中内吞吸收营养物质的必需细胞器。详细的分析表明,Kelch13 定位于细胞器的致密颈部,并且作为微孔内吞摄取的蛋白质枢纽发挥作用。有趣的是,微孔的最大活性需要寄生虫中神经酰胺从头合成途径。因此,这项研究为顶复门寄生虫获取宿主细胞来源的营养物质的机制提供了深入的了解,这些营养物质原本是与宿主细胞隔离开来的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a466/9947163/c43a9912427c/41467_2023_36571_Fig1_HTML.jpg

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