title: Identification of a Plasmodium falciparum phospholipid transfer protein.
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.
authors.affiliation: From the Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom.
authors.forename: Christiaan
authors.initials: C
authors.lastname: van Ooij
authors.forename: Chrislaine
authors.initials: C
authors.lastname: Withers-Martinez
authors.forename: Alessa
authors.initials: A
authors.lastname: Ringel
authors.forename: Shamshad
authors.initials: S
authors.lastname: Cockcroft
authors.forename: Kasturi
authors.initials: K
authors.lastname: Haldar
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blackman
mesh_terms: D001693:Biological Transport, Active; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D018922:HL-60 Cells; D006801:Humans; D008563:Membrane Lipids / Q000235:genetics / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism / Q000469:parasitology
chemical_list: D008563:Membrane Lipids; D049294:Phospholipid Transfer Proteins; D015800:Protozoan Proteins
keywords: Lipid Transport; Malaria; Parasitology; Phospholipid; Phospholipid Transfer; Plasmodium
references.citation: J Biol Chem. 1996 Aug 30;271(35):21075-80
references.pmid: 8702874
references.citation: J Mol Biol. 1999 Apr 9;287(4):797-815
references.pmid: 10191147
references.citation: Bioinformatics. 2009 Jul 15;25(14):1761-7
references.pmid: 19429599
references.citation: Mol Microbiol. 2010 Apr;76(1):12-24
references.pmid: 20141604
references.citation: Mol Microbiol. 2003 Nov;50(4):1215-27
references.pmid: 14622410
references.citation: Cell Host Microbe. 2012 Nov 15;12(5):717-29
references.pmid: 23159060
references.citation: Science. 2004 Dec 10;306(5703):1934-7
references.pmid: 15591203
references.citation: Exp Parasitol. 1971 Oct;30(2):284-320
references.pmid: 4399774
references.citation: PLoS Pathog. 2008 Jun 13;4(6):e1000084
references.pmid: 18551176
references.citation: Exp Parasitol. 1994 Nov;79(3):250-9
references.pmid: 7957747
references.citation: Mol Biochem Parasitol. 1985 Nov;17(2):239-51
references.pmid: 3906394
references.citation: Exp Parasitol. 1994 Nov;79(3):260-9
references.pmid: 7957748
references.citation: Mol Microbiol. 2013 Feb;87(4):835-50
references.pmid: 23279267
references.citation: Mol Cell Biol. 2006 Jun;26(11):4074-85
references.pmid: 16705161
references.citation: PLoS Pathog. 2011 Sep;7(9):e1002198
references.pmid: 21909260
references.citation: Nat Methods. 2006 Aug;3(8):615-21
references.pmid: 16862136
references.citation: Eur J Cell Biol. 2003 Jun;82(6):271-84
references.pmid: 12868595
references.citation: Nat Rev Microbiol. 2009 May;7(5):341-54
references.pmid: 19369950
references.citation: Structure. 2004 Feb;12(2):317-26
references.pmid: 14962392
references.citation: Nature. 2002 Oct 3;419(6906):520-6
references.pmid: 12368866
references.citation: Mol Biochem Parasitol. 1991 Nov;49(1):35-44
references.pmid: 1723148
references.citation: Genome Biol. 2006;7(2):R12
references.pmid: 16507167
references.citation: Eur J Cell Biol. 2004 Oct;83(10):567-82
references.pmid: 15679102
references.citation: PLoS Pathog. 2013 May;9(5):e1003344
references.pmid: 23675297
references.citation: Int J Mol Sci. 2013 Mar 18;14(3):6170-86
references.pmid: 23507753
references.citation: J Biol Chem. 2010 Mar 5;285(10):7358-65
references.pmid: 20042613
references.citation: Cell Microbiol. 2010 Oct;12(10):1398-420
references.pmid: 20482550
references.citation: PLoS Pathog. 2011 Jun;7(6):e1002092
references.pmid: 21731489
references.citation: Trends Parasitol. 2010 Jan;26(1):6-10
references.pmid: 19879191
references.citation: Biochim Biophys Acta. 2007 Jun;1771(6):654-62
references.pmid: 17499021
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D539-43
references.pmid: 18957442
references.citation: J Biol Chem. 2005 Jul 22;280(29):27436-42
references.pmid: 15911624
references.citation: PLoS One. 2011;6(6):e19521
references.pmid: 21738568
references.citation: Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):531-6
references.pmid: 23267069
references.citation: J Proteomics. 2011 Aug 24;74(9):1701-10
references.pmid: 21515433
references.citation: Mol Cell Proteomics. 2010 Jul;9(7):1437-48
references.pmid: 20332084
references.citation: Biochim Biophys Acta. 2002 Jan 30;1580(1):67-76
references.pmid: 11923101
references.citation: Science. 1997 May 16;276(5315):1122-5
references.pmid: 9148808
references.citation: J Endocrinol. 2012 Mar;212(3):257-75
references.pmid: 21965545
references.citation: Lancet. 2012 Feb 4;379(9814):413-31
references.pmid: 22305225
references.citation: Biochemistry. 1981 Jan 6;20(1):146-51
references.pmid: 7470465
references.citation: Biochim Biophys Acta. 2012 Mar;1818(3):425-33
references.pmid: 22063720
references.citation: Blood. 1989 Aug 1;74(2):855-61
references.pmid: 2665857
references.citation: Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
references.pmid: 9254694
references.citation: PLoS Biol. 2003 Oct;1(1):E5
references.pmid: 12929205
references.citation: Biochem J. 2002 Aug 15;366(Pt 1):23-34
references.pmid: 12023904
references.citation: Mol Biochem Parasitol. 2005 Aug;142(2):258-62
references.pmid: 15951034
references.citation: Biochem J. 1996 Apr 1;315 ( Pt 1):307-14
references.pmid: 8670123
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):488-93
references.pmid: 18184806
references.citation: Biochim Biophys Acta. 1985 Sep 11;836(2):176-84
references.pmid: 2411293
references.citation: Science. 2004 Dec 10;306(5703):1930-3
references.pmid: 15591202
references.citation: Biochem Biophys Res Commun. 2004 Jan 30;314(1):181-5
references.pmid: 14715263
references.citation: PLoS One. 2011 Mar 31;6(3):e18396
references.pmid: 21483790
references.citation: Mol Biochem Parasitol. 2008 Aug;160(2):107-15
references.pmid: 18534695
references.citation: Nat Struct Biol. 2002 Jul;9(7):507-11
references.pmid: 12055623
references.citation: Adv Parasitol. 2001;50:1-86
references.pmid: 11757330
references.citation: Nucleic Acids Res. 2006 Feb 21;34(4):1166-73
references.pmid: 16493140