Identification of a Plasmodium falciparum Phospholipid Transfer Protein
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Authors: | Christiaan van Ooij Chrislaine Withers-Martinez Alessa Ringel Shamshad Cockcroft Kasturi Haldar Michael J Blackman |
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Institution: | From the ‡Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom.;the §Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6JJ, United Kingdom, and ;the ¶Center for Rare and Neglected Diseases and Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556 |
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Abstract: | Infection of erythrocytes by the human malaria parasite Plasmodium falciparum results in dramatic modifications to the host cell, including changes to its antigenic and transport properties and the de novo formation of membranous compartments within the erythrocyte cytosol. These parasite-induced structures are implicated in the transport of nutrients, metabolic products, and parasite proteins, as well as in parasite virulence. However, very few of the parasite effector proteins that underlie remodeling of the host erythrocyte are functionally characterized. Using bioinformatic examination and modeling, we have found that the exported P. falciparum protein PFA0210c belongs to the START domain family, members of which mediate transfer of phospholipids, ceramide, or fatty acids between membranes. In vitro phospholipid transfer assays using recombinant PFA0210 confirmed that it can transfer phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin between phospholipid vesicles. Furthermore, assays using HL60 cells containing radiolabeled phospholipids indicated that orthologs of PFA0210c can also transfer phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine. Biochemical and immunochemical analysis showed that PFA0210c associates with membranes in infected erythrocytes at mature stages of intracellular parasite growth. Localization studies in live parasites revealed that the protein is present in the parasitophorous vacuole during growth and is later recruited to organelles in the parasite. Together these data suggest that PFA0210c plays a role in the formation of the membranous structures and nutrient phospholipid transfer in the malaria-parasitized erythrocyte. |
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Keywords: | Lipid Transport Malaria Parasitology Phospholipid Plasmodium Phospholipid Transfer |
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