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

被引:30
作者
Ehrenman, Karen [1 ]
Sehgal, Alfica [2 ]
Lige, Bao [1 ]
Stedman, Timothy T. [3 ]
Joiner, Keith A. [4 ]
Coppens, Isabelle [1 ]
机构
[1] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Dept Cell Biol, Sch Med, Baltimore, MD 21205 USA
[3] Malaria Reference & Res Reagent Resource Ctr, Manassas, VA 20110 USA
[4] Univ Arizona, Coll Med, Arizona Hlth Sci Ctr, Tucson, AZ 85724 USA
关键词
PARASITOPHOROUS VACUOLE; CHOLESTEROL TRANSPORT; ABCG TRANSPORTERS; TANGIER-DISEASE; GONDII; SECRETION; SUPERFAMILY; RESISTANCE; MEMBRANE; EFFLUX;
D O I
10.1111/j.1365-2958.2010.07169.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
P>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.
引用
收藏
页码:1232 / 1249
页数:18
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