GRA47 对弓形虫寄生泡的形态和渗透性非常重要。

IF 3.7 2区 医学 Q1 PARASITOLOGY
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引用次数: 0

摘要

建立一个完整的细胞内寄生虫液泡(PV),使其能够有效地摄取营养物质和贩运蛋白质,对于弓形虫的生存和增殖至关重要。虽然PV膜(PVM)定位的致密颗粒蛋白17(GRA17)和GRA23介导了PVM对小分子的通透性,包括营养物质的摄取和代谢副产物的排泄,但弓形虫获取营养物质的分子机制仍不清楚。在这项研究中,我们发现分泌蛋白 GRA47 对淋病双球菌正常的 PV 形态、PVM 对小分子的通透性、生长和毒力都有贡献。共免疫沉淀分析表明 GRA47 与 GRA72 有潜在的相互作用,而 GRA72 的缺失会影响 PV 形态、寄生虫的生长和感染性。为了研究 GRA47、GRA72、GRA17 和 GRA23 之间的生物学关系,尝试构建了双基因缺失株和过表达株。结果只成功构建了Δgra23Δgra72。与 Δgra23 株系相比,该株系的异常 PV 比例明显增加。过表达三个相关 GRA 中的一个可部分修复 Δgra47、Δgra72 和 Δgra17 中形态异常的 PV,而表达恶性疟原虫 PVM 蛋白 PfExp2(GRA17 和 GRA23 的直系同源物)可完全修复所有三个 Δgra 株系中的 PV 形态缺陷。这些结果表明,这三种 GRA 蛋白可能并非功能冗余,而是以不同的方式调节营养物质的获取。这些发现凸显了淋球菌营养摄取机制的多样性,这可能是淋球菌能够在多种宿主的不同细胞环境中生长的重要原因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

GRA47 is important for the morphology and permeability of the parasitophorous vacuole in Toxoplasma gondii

GRA47 is important for the morphology and permeability of the parasitophorous vacuole in Toxoplasma gondii

GRA47 is important for the morphology and permeability of the parasitophorous vacuole in Toxoplasma gondii

Establishing an intact intracellular parasitophorous vacuole (PV) that enables efficient nutrient uptake and protein trafficking is essential for the survival and proliferation of Toxoplasma gondii. Although the PV membrane (PVM)-localized dense granule protein 17 (GRA17) and GRA23 mediate the permeability of the PVM to small molecules, including nutrient uptake and excretion of metabolic by-products, the molecular mechanism by which T. gondii acquires nutrients remains unclear. In this study, we showed that the secreted protein GRA47 contributed to normal PV morphology, PVM permeability to small molecules, growth, and virulence in T. gondii. Co-immunoprecipitation analysis demonstrated potential interaction of GRA47 with GRA72, and the loss of GRA72 affected PV morphology, parasite growth and infectivity. To investigate the biological relationship among GRA47, GRA72, GRA17 and GRA23, attempts were made to construct strains with double gene deletion and overexpressing strains. Only Δgra23Δgra72 was successfully constructed. This strain exhibited a significant increase in the proportion of aberrant PVs compared with the Δgra23 strain. Overexpressing one of the three related GRAs partially rescued PVs with aberrant morphology in Δgra47, Δgra72 and Δgra17, while the expression of the Plasmodium falciparum PVM protein PfExp2, an ortholog of GRA17 and GRA23, fully rescued the PV morphological defect in all three Δgra strains. These results suggest that these GRA proteins may not be functionally redundant but rather work in different ways to regulate nutrient acquisition. These findings highlight the versatility of the nutrient uptake mechanisms in T. gondii, which may contribute to the parasite’s remarkable ability to grow in different cellular niches in a very broad range of hosts.

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来源期刊
CiteScore
8.40
自引率
2.50%
发文量
76
审稿时长
23 days
期刊介绍: International Journal for Parasitology offers authors the option to sponsor nonsubscriber access to their articles on Elsevier electronic publishing platforms. For more information please view our Sponsored Articles page. The International Journal for Parasitology publishes the results of original research in all aspects of basic and applied parasitology, including all the fields covered by its Specialist Editors, and ranging from parasites and host-parasite relationships of intrinsic biological interest to those of social and economic importance in human and veterinary medicine and agriculture.
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