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三磷酸腺苷结合盒 G 型转运蛋白在弓形虫脂质重分布中的新作用。

Novel roles for ATP-binding cassette G transporters in lipid redistribution in Toxoplasma.

机构信息

Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.

出版信息

Mol Microbiol. 2010 Jun 1;76(5):1232-49. doi: 10.1111/j.1365-2958.2010.07169.x. Epub 2010 May 12.

Abstract

Toxoplasma is a protozoan parasite proficiently adapted to thrive in a parasitophorous vacuole (PV) formed in the cytoplasm of a large variety of mammalian cells. As an actively dividing organism, the parasite must adjust the lipid composition of its membranes to preserve organelle vitality and expand the size of the PV membrane to accommodate growing progeny. We showed that Toxoplasma takes up host lipids and can expel major lipids in an ATP-dependent process. In order to provide detailed mechanistic insights into lipid trafficking phenomena relevant to Toxoplasma biology, we characterized six parasite ATP-binding cassette (ABC) G family transporters and investigated their potential contribution to lipid homeostatic processes. All these transporters are expressed in the parasite and five of them are upregulated upon exposure to sterols. Four ABCG are localized to secretory organelles and the plasma membrane, and promote cholesterol and phospholipid efflux, reflecting the importance in exportation of large amounts of lipids into the PV. Interestingly, one ABCG that is associated with vesicles in the PV and the plasma membrane acts as a cholesterol importer. This last finding expands our current view on the role of some ABCG transporters in eukaryotic sterol influx.

摘要

刚地弓形虫是一种原生动物寄生虫,能够在细胞质中形成的寄生空泡(PV)中茁壮成长,这种空泡存在于多种哺乳动物细胞中。作为一种活跃分裂的生物,寄生虫必须调整其膜的脂质组成,以保持细胞器活力并扩大 PV 膜的大小,以容纳不断生长的后代。我们发现,弓形虫可以摄取宿主脂质,并通过 ATP 依赖的过程排出主要脂质。为了深入了解与弓形虫生物学相关的脂质运输现象的详细机制,我们对六种寄生虫 ATP 结合盒(ABC)G 家族转运蛋白进行了表征,并研究了它们在脂质稳态过程中的潜在作用。所有这些转运蛋白在寄生虫中表达,其中五种在暴露于固醇时被上调。四个 ABCG 定位于分泌细胞器和质膜,并促进胆固醇和磷脂外排,这反映了将大量脂质输出到 PV 中的重要性。有趣的是,一个与 PV 和质膜中的囊泡相关的 ABCG 作为胆固醇的内流体。这一最后发现扩展了我们目前对一些 ABCG 转运蛋白在真核生物固醇内流中的作用的认识。

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