title: Transport of fluorescent phospholipid analogues from the erythrocyte membrane to the parasite in Plasmodium falciparum-infected cells.
abstract: The asexual development of the human malaria parasite Plasmodium falciparum is largely intraerythrocytic. When 1-palmitoyl-2-[6-[(7-nitro-2-1,3-benzoxadiazole-4-yl)amino]caproyl] phosphatidylcholine (NBD-PC) was incorporated into infected and uninfected erythrocyte membranes at 0 degrees C, it remained at the cell surface. At 10 degrees C, the lipid was rapidly internalized in infected erythrocytes at all stages of parasite growth. Our results indicate that the internalization of NDB-PC was not because of endocytosis but rapid transbilayer lipid flip-flop at the infected erythrocyte membrane, followed by monomer diffusion to the parasite. Internalization of the lipid was inhibited by (a) depleting cellular ATP levels; (b) pretreating the cells with N-ethyl maleimide or diethylpyrocarbonate; and (c) 10 mM L-alpha-glycerophosphorylcholine. The evidence suggests protein-mediated and energy dependent transmembrane movement of the PC analogue. The conditions for the internalization of another phospholipid analogue N-4-nitrobenzo-2-oxa-1,3-diazoledipalmitoyl phosphatidylethanolamine (N-NBD-PE) were distinct from that of NBD-PC and suggest the presence of additional mechanism(s) of parasite-mediated lipid transport in the infected host membrane. In spite of the lack of bulk, constitutive endocytosis at the red cell membrane, the uptake of Lucifer yellow by mature infected cells suggests that microdomains of pinocytotic activity are induced by the intracellular parasite. The results indicate the presence of parasite-induced mechanisms of lipid transport in infected erythrocyte membranes that modify host membrane properties and may have important implications on phospholipid asymmetry in these membranes.
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305.
authors.forename: K
authors.initials: K
authors.lastname: Haldar
authors.forename: A F
authors.initials: AF
authors.lastname: de Amorim
authors.forename: G A
authors.initials: GA
authors.lastname: Cross
mesh_terms: D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D001693:Biological Transport, Active; D002451:Cell Compartmentation; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology*; D005456:Fluorescent Dyes; D006801:Humans; D007546:Isoquinolines; D008563:Membrane Lipids / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010713:Phosphatidylcholines / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D010873:Pinocytosis; D010963:Plasmodium falciparum / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D005456:Fluorescent Dyes; D007546:Isoquinolines; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C017475:lucifer yellow