title: Novel roles for ATP-binding cassette G transporters in lipid redistribution in Toxoplasma.
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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Ehrenman
authors.forename: Alfica
authors.initials: A
authors.lastname: Sehgal
authors.forename: Bao
authors.initials: B
authors.lastname: Lige
authors.forename: Timothy T
authors.initials: TT
authors.lastname: Stedman
authors.forename: Keith A
authors.initials: KA
authors.lastname: Joiner
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coppens
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D019556:COS Cells; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002522:Chlorocebus aethiops; D006790:Host-Parasite Interactions; D006801:Humans; D050356:Lipid Metabolism; D008969:Molecular Sequence Data; D030781:Organisms, Genetically Modified; D010743:Phospholipids / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013261:Sterols / Q000378:metabolism; D014122:Toxoplasma / Q000166:cytology / Q000235:genetics / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D010743:Phospholipids; D020033:Protein Isoforms; D015800:Protozoan Proteins; D013261:Sterols