Logo of jcellbiolHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Cell Biol. 1989 Jun 1; 108(6): 2183–2192.
PMCID: PMC2115588

Transport of fluorescent phospholipid analogues from the erythrocyte membrane to the parasite in Plasmodium falciparum-infected cells


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.

Full Text

The Full Text of this article is available as a PDF (2.2M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bishop WR, Bell RM. Assembly of the endoplasmic reticulum phospholipid bilayer: the phosphatidylcholine transporter. Cell. 1985 Aug;42(1):51–60. [PubMed]
  • Connor J, Schroit AJ. Transbilayer movement of phosphatidylserine in erythrocytes: inhibition of transport and preferential labeling of a 31,000-dalton protein by sulfhydryl reactive reagents. Biochemistry. 1988 Feb 9;27(3):848–851. [PubMed]
  • Coppel RL, Culvenor JG, Bianco AE, Crewther PE, Stahl HD, Brown GV, Anders RF, Kemp DJ. Variable antigen associated with the surface of erythrocytes infected with mature stages of Plasmodium falciparum. Mol Biochem Parasitol. 1986 Sep;20(3):265–277. [PubMed]
  • Cranston HA, Boylan CW, Carroll GL, Sutera SP, Williamson JR, Gluzman IY, Krogstad DJ. Plasmodium falciparum maturation abolishes physiologic red cell deformability. Science. 1984 Jan 27;223(4634):400–403. [PubMed]
  • Daleke DL, Huestis WH. Incorporation and translocation of aminophospholipids in human erythrocytes. Biochemistry. 1985 Sep 24;24(20):5406–5416. [PubMed]
  • Divo AA, Geary TG, Jensen JB, Ginsburg H. The mitochondrion of Plasmodium falciparum visualized by rhodamine 123 fluorescence. J Protozool. 1985 Aug;32(3):442–446. [PubMed]
  • Ginsburg H, Kutner S, Krugliak M, Cabantchik ZI. Characterization of permeation pathways appearing in the host membrane of Plasmodium falciparum infected red blood cells. Mol Biochem Parasitol. 1985 Mar;14(3):313–322. [PubMed]
  • Gupta CM, Mishra GC. Transbilayer phospholipid asymmetry in Plasmodium knowlesi-infected host cell membrane. Science. 1981 May 29;212(4498):1047–1049. [PubMed]
  • Gupta CM, Alam A, Mathur PN, Dutta GP. A new look at nonparasitized red cells of malaria-infected monkeys. Nature. 1982 Sep 16;299(5880):259–261. [PubMed]
  • Haldar K, Henderson CL, Cross GA. Identification of the parasite transferrin receptor of Plasmodium falciparum-infected erythrocytes and its acylation via 1,2-diacyl-sn-glycerol. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8565–8569. [PMC free article] [PubMed]
  • Howard RJ, Lyon JA, Uni S, Saul AJ, Aley SB, Klotz F, Panton LJ, Sherwood JA, Marsh K, Aikawa M, et al. Transport of an Mr approximately 300,000 Plasmodium falciparum protein (Pf EMP 2) from the intraerythrocytic asexual parasite to the cytoplasmic face of the host cell membrane. J Cell Biol. 1987 May;104(5):1269–1280. [PMC free article] [PubMed]
  • Joshi P, Alam A, Chandra R, Puri SK, Gupta CM. Possible basis for membrane changes in nonparasitized erythrocytes of malaria-infected animals. Biochim Biophys Acta. 1986 Nov 6;862(1):220–222. [PubMed]
  • Kimmich GA, Randles J, Brand JS. Assay of picomole amounts of ATP, ADP, and AMP using the luciferase enzyme system. Anal Biochem. 1975 Nov;69(1):187–206. [PubMed]
  • Kutner S, Baruch D, Ginsburg H, Cabantchik ZI. Alterations in membrane permeability of malaria-infected human erythrocytes are related to the growth stage of the parasite. Biochim Biophys Acta. 1982 Apr 23;687(1):113–117. [PubMed]
  • Langreth SG, Jensen JB, Reese RT, Trager W. Fine structure of human malaria in vitro. J Protozool. 1978 Nov;25(4):443–452. [PubMed]
  • Leech JH, Barnwell JW, Miller LH, Howard RJ. Identification of a strain-specific malarial antigen exposed on the surface of Plasmodium falciparum-infected erythrocytes. J Exp Med. 1984 Jun 1;159(6):1567–1575. [PMC free article] [PubMed]
  • Martin OC, Pagano RE. Transbilayer movement of fluorescent analogs of phosphatidylserine and phosphatidylethanolamine at the plasma membrane of cultured cells. Evidence for a protein-mediated and ATP-dependent process(es). J Biol Chem. 1987 Apr 25;262(12):5890–5898. [PubMed]
  • Moll GN, Vial HJ, Ancelin ML, Op den Kamp JA, Roelofsen B, van Deenen LL. Phospholipid uptake by Plasmodium knowlesi infected erythrocytes. FEBS Lett. 1988 May 23;232(2):341–346. [PubMed]
  • Op den Kamp JA. Lipid asymmetry in membranes. Annu Rev Biochem. 1979;48:47–71. [PubMed]
  • Pollack S, Fleming J. Plasmodium falciparum takes up iron from transferrin. Br J Haematol. 1984 Oct;58(2):289–293. [PubMed]
  • Rimon G, Meyerstein N, Henis YI. Lateral mobility of phospholipids in the external and internal leaflets of normal and hereditary spherocytic human erythrocytes. Biochim Biophys Acta. 1984 Sep 5;775(3):283–290. [PubMed]
  • Rodriguez MH, Jungery M. A protein on Plasmodium falciparum-infected erythrocytes functions as a transferrin receptor. Nature. 324(6095):388–391. [PubMed]
  • Schroit AJ, Madsen JW, Tanaka Y. In vivo recognition and clearance of red blood cells containing phosphatidylserine in their plasma membranes. J Biol Chem. 1985 Apr 25;260(8):5131–5138. [PubMed]
  • Schwartz RS, Olson JA, Raventos-Suarez C, Yee M, Heath RH, Lubin B, Nagel RL. Altered plasma membrane phospholipid organization in Plasmodium falciparum-infected human erythrocytes. Blood. 1987 Feb;69(2):401–407. [PubMed]
  • Seigneuret M, Devaux PF. ATP-dependent asymmetric distribution of spin-labeled phospholipids in the erythrocyte membrane: relation to shape changes. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3751–3755. [PMC free article] [PubMed]
  • Sheetz MP, Schindler M, Koppel DE. Lateral mobility of integral membrane proteins is increased in spherocytic erythrocytes. Nature. 1980 Jun 12;285(5765):510–511. [PubMed]
  • Sleight RG, Pagano RE. Transport of a fluorescent phosphatidylcholine analog from the plasma membrane to the Golgi apparatus. J Cell Biol. 1984 Aug;99(2):742–751. [PMC free article] [PubMed]
  • Sleight RG, Pagano RE. Transbilayer movement of a fluorescent phosphatidylethanolamine analogue across the plasma membranes of cultured mammalian cells. J Biol Chem. 1985 Jan 25;260(2):1146–1154. [PubMed]
  • Stanley HA, Reese RT. Plasmodium falciparum polypeptides associated with the infected erythrocyte plasma membrane. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6093–6097. [PMC free article] [PubMed]
  • Tanaka Y, Schroit AJ. Insertion of fluorescent phosphatidylserine into the plasma membrane of red blood cells. Recognition by autologous macrophages. J Biol Chem. 1983 Sep 25;258(18):11335–11343. [PubMed]
  • Taraschi TF, Parashar A, Hooks M, Rubin H. Perturbation of red cell membrane structure during intracellular maturation of Plasmodium falciparum. Science. 1986 Apr 4;232(4746):102–104. [PubMed]
  • Tilley L, Cribier S, Roelofsen B, Op den Kamp JA, van Deenen LL. ATP-dependent translocation of amino phospholipids across the human erythrocyte membrane. FEBS Lett. 1986 Jan 1;194(1):21–27. [PubMed]
  • Trager W, Jensen JB. Human malaria parasites in continuous culture. Science. 1976 Aug 20;193(4254):673–675. [PubMed]
  • Udomsangpetch R, Lundgren K, Berzins K, Wåhlin B, Perlmann H, Troye-Blomberg M, Carlsson J, Wahlgren M, Perlmann P, Björkman A. Human monoclonal antibodies to Pf 155, a major antigen of malaria parasite Plasmodium falciparum. Science. 1986 Jan 3;231(4733):57–59. [PubMed]
  • Van der Schaft PH, Beaumelle B, Vial H, Roelofsen B, Op den Kamp JA, Van Deenen LL. Phospholipid organization in monkey erythrocytes upon Plasmodium knowlesi infection. Biochim Biophys Acta. 1987 Jul 10;901(1):1–14. [PubMed]
  • Vernot-Hernandez JP, Heidrich HG. Time-course of synthesis, transport and incorporation of a protein identified in purified membranes of host erythrocytes infected with a knob-forming strain of Plasmodium falciparum. Mol Biochem Parasitol. 1984 Jul;12(3):337–350. [PubMed]
  • Vial HJ, Thuet MJ, Broussal JL, Philippot JR. Phospholipid biosynthesis by Plasmodium knowlesi-infected erythrocytes: the incorporation of phospohlipid precursors and the identification of previously undetected metabolic pathways. J Parasitol. 1982 Jun;68(3):379–391. [PubMed]
  • Zachowski A, Favre E, Cribier S, Hervé P, Devaux PF. Outside-inside translocation of aminophospholipids in the human erythrocyte membrane is mediated by a specific enzyme. Biochemistry. 1986 May 6;25(9):2585–2590. [PubMed]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.
  • Taxonomy
    Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
  • Taxonomy Tree
    Taxonomy Tree

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...