scholarly journals Trafficking and Association of Plasmodium falciparum MC-2TM with the Maurer’s Clefts

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 431
Author(s):  
Raghavendra Yadavalli ◽  
John W. Peterson ◽  
Judith A. Drazba ◽  
Tobili Y. Sam-Yellowe
Keyword(s):  
Plasmodium Falciparum ◽  
Erythrocyte Membrane ◽  
Sodium Carbonate ◽  
Infected Erythrocyte ◽  
Brefeldin A ◽  
Specific Expression ◽  
Lipid Interactions ◽  
And Topology ◽  
Streptolysin O ◽  
Maurer's Clefts

In this study, we investigated stage specific expression, trafficking, solubility and topology of endogenous PfMC-2TM in P. falciparum (3D7) infected erythrocytes. Following Brefeldin A (BFA) treatment of parasites, PfMC-2TM traffic was evaluated using immunofluorescence with antibodies reactive with PfMC-2TM. PfMC-2TM is sensitive to BFA treatment and permeabilization of infected erythrocytes with streptolysin O (SLO) and saponin, showed that the N and C-termini of PfMC-2TM are exposed to the erythrocyte cytoplasm with the central portion of the protein protected in the MC membranes. PfMC-2TM was expressed as early as 4 h post invasion (hpi), was tightly colocalized with REX-1 and trafficked to the erythrocyte membrane without a change in solubility. PfMC-2TM associated with the MC and infected erythrocyte membrane and was resistant to extraction with alkaline sodium carbonate, suggestive of protein-lipid interactions with membranes of the MC and erythrocyte. PfMC-2TM is an additional marker of the nascent MCs.

scholarly journals Role of the Plasmodium falciparum mature-parasite-infected erythrocyte surface antigen (MESA/PfEMP-2) in malarial infection of erythrocytes

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 3196-3204 ◽  
Author(s):  
C Magowan ◽  
RL Coppel ◽  
AO Lau ◽  
MM Moronne ◽  
G Tchernia ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Erythrocyte Membrane ◽  
Surface Antigen ◽  
Infected Erythrocyte ◽  
Spontaneous Mutant ◽  
Protein 4.1 ◽  
Erythrocyte Surface ◽  
Skeletal Protein ◽  
Parasite Viability

Abstract During intraerythrocytic growth of Plasmodium falciparum, several parasite proteins are transported from the parasite to the erythrocyte membrane, where they bind to membrane skeletal proteins. Mature-parasite-infected erythrocyte surface antigen (MESA) has previously been shown to associate with host erythrocyte membrane skeletal protein 4.1. Using a spontaneous mutant of P falciparum that has lost the ability to synthesize MESA and 4.1-deficient erythrocytes, we examined growth of MESA(+) and MESA(-) parasites in normal and 4.1-deficient erythrocytes. Viability of MESA(+) parasites was reduced in 4.1-deficient erythrocytes as compared with that for normal erythrocytes, but MESA(-) parasites grew equally well in 4.1-deficient and normal erythrocytes. Cytoadherence of MESA(+)- and MESA (-)-parasitized normal and 4.1-deficient erythrocytes to C32 melanoma cells was similar, indicating that neither protein 4.1 nor MESA plays a major role in cytoadherence of infected erythrocytes. Localization of MESA in normal and 4.1-deficient erythrocytes was examined by confocal microscopy. MESA was diffusely distributed in the cytosol of 4.1-deficient erythrocytes but was membrane-associated in normal erythrocytes. These findings suggest that MESA binding to protein 4.1 plays a major role in intraerythrocytic parasite viability.

scholarly journals Delivery of the Malaria Virulence Protein PfEMP1 to the Erythrocyte Surface Requires Cholesterol-Rich Domains

2006 ◽  
Vol 5 (5) ◽  
pp. 849-860 ◽  
Author(s):  
Sarah Frankland ◽  
Akinola Adisa ◽  
Paul Horrocks ◽  
Theodore F. Taraschi ◽  
Timothy Schneider ◽  
...  
Keyword(s):  
Erythrocyte Membrane ◽  
Infected Erythrocyte ◽  
Membrane Microdomains ◽  
Human Malaria Parasite ◽  
Vesicle Budding ◽  
Erythrocyte Invasion ◽  
Major Virulence Factor ◽  
Erythrocyte Surface ◽  
Virulence Protein ◽  
Maurer's Clefts

ABSTRACT The particular virulence of the human malaria parasite Plasmodium falciparum derives from export of parasite-encoded proteins to the surface of the mature erythrocytes in which it resides. The mechanisms and machinery for the export of proteins to the erythrocyte membrane are largely unknown. In other eukaryotic cells, cholesterol-rich membrane microdomains or “rafts” have been shown to play an important role in the export of proteins to the cell surface. Our data suggest that depletion of cholesterol from the erythrocyte membrane with methyl-β-cyclodextrin significantly inhibits the delivery of the major virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1). The trafficking defect appears to lie at the level of transfer of PfEMP1 from parasite-derived membranous structures within the infected erythrocyte cytoplasm, known as the Maurer's clefts, to the erythrocyte membrane. Thus our data suggest that delivery of this key cytoadherence-mediating protein to the host erythrocyte membrane involves insertion of PfEMP1 at cholesterol-rich microdomains. GTP-dependent vesicle budding and fusion events are also involved in many trafficking processes. To determine whether GTP-dependent events are involved in PfEMP1 trafficking, we have incorporated non-membrane-permeating GTP analogs inside resealed erythrocytes. Although these nonhydrolyzable GTP analogs reduced erythrocyte invasion efficiency and partially retarded growth of the intracellular parasite, they appeared to have little direct effect on PfEMP1 trafficking.

scholarly journals Characterization of the choline carrier of Plasmodium falciparum: a route for the selective delivery of novel antimalarial drugs

Blood ◽  
2004 ◽  
Vol 104 (10) ◽  
pp. 3372-3377 ◽  
Author(s):  
Giancarlo A. Biagini ◽  
Erica M. Pasini ◽  
Ruth Hughes ◽  
Harry P. De Koning ◽  
Henri J. Vial ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Erythrocyte Membrane ◽  
Infected Erythrocyte ◽  
Antimalarial Drugs ◽  
New Drugs ◽  
Erythrocyte Membranes ◽  
Great Promise ◽  
Intracellular Parasite ◽  
Choline Transporter

Abstract New drugs are urgently needed to combat the growing problem of drug resistance in Plasmodium falciparum malaria. The infected erythrocyte is a multicompartmental system, and its transporters are of interest as drug targets in their own right and as potential routes for the delivery of antimalarial drugs. Choline is an important nutrient that penetrates infected erythrocyte membranes through the endogenous carrier and through parasite-induced permeability pathways, but nothing is known about its transport into the intracellular parasite. Here we present the first characterization of choline transport across the parasite membrane. Transport exhibits Michaelis-Menten kinetics with an apparent Km of 25.0 ± 3.5 μM for choline. The carrier is inhibitor-sensitive, temperature-dependent, and Na+-independent, and it is driven by the proton-motive force. Highly active bis-amidine and bis-quaternary ammonium compounds are also known to penetrate the host erythrocyte membrane through parasite-induced permeability pathways. Here, we demonstrate that the parasite choline transporter mediates the delivery of these compounds to the intracellular parasite. Thus, the induced permeability pathways in the host erythrocyte membrane and the parasite choline transporter described here form a cooperative transport system that shows great promise for the selective targeting of new agents for the chemotherapy of malaria. (Blood. 2004;104: 3372-3377)

scholarly journals High Prevalence of Human Antibodies to Recombinant Duffy Binding-Like α Domains of the Plasmodium falciparum-Infected Erythrocyte Membrane Protein 1 in Semi-Immune Adults Compared to That in Nonimmune Children

2001 ◽  
Vol 69 (12) ◽  
pp. 7603-7609 ◽  
Author(s):  
Raphael M. Oguariri ◽  
Steffen Borrmann ◽  
Mo-Quen Klinkert ◽  
Peter G. Kremsner ◽  
Jürgen F. J. Kun
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Erythrocyte Membrane ◽  
Fusion Proteins ◽  
Infected Erythrocyte ◽  
Antibody Responses ◽  
Antibody Activity ◽  
Serum Samples ◽  
Erythrocyte Membrane Protein ◽  
High Level

ABSTRACT We used a panel of nine fusion proteins that contain different Duffy binding-like α (DBL-α) domains ofPlasmodium falciparum-infected erythrocyte membrane protein 1 to assess the levels of antibody activity in serum samples obtained from semi-immune or nonimmune individuals from Lambaréné, Gabon. Recognition was measured in terms of either the prevalence or the magnitude of the response. A strong correlation between the immune status of the patients and reactivity with recombinant proteins was observed, which was interpreted as a reflection of the number of infections acquired over time. The antibody responses were predominantly directed toward variable epitopes of the DBL-α domain. Antibody responses could be reduced by preincubation of the sera with various fusion proteins. A portion of individuals who exhibited high-level responses to all fusion proteins also had antibodies which recognized conserved epitopes. The possibility that a synergizing effect of anti-DBL-α domain antibodies could support chemotherapy is discussed.

scholarly journals Plasmodium falciparum-infected erythrocytes utilize a synthetic truncated ceramide precursor for synthesis and secretion of truncated sphingomyelin

1995 ◽  
Vol 308 (1) ◽  
pp. 335-341 ◽  
Author(s):  
I Ansorge ◽  
D Jeckel ◽  
F Wieland ◽  
K Lingelbach
Keyword(s):  
Plasmodium Falciparum ◽  
Mammalian Cells ◽  
Membrane Fraction ◽  
Infected Erythrocyte ◽  
Brefeldin A ◽  
Parasite Development ◽  
Phospholipid Content ◽  
Unicellular Eukaryote ◽  
Fungal Metabolite ◽  
Sphingomyelin Synthase

Plasmodium falciparum is an intracellular parasite of human erythrocytes. Parasite development is accompanied by an increase of the phospholipid content of the infected erythrocyte, but it results in a selective decrease of sphingomyelin. We have studied sphingomyelin biosynthesis in infected erythrocytes using as substrate a synthetic radiolabelled ceramide precursor, truncated in both hydrophobic chains. Lysates of infected, unlike those of non-infected, erythrocytes contained sphingomyelin synthase activity, which therefore is of parasite origin. The enzyme activity was associated with a membrane fraction. In contrast to mammalian cells, the parasite did not synthesize detectable levels of glycosphingolipids. In intact infected erythrocytes the ceramide precursor was converted into a correspondingly truncated soluble sphingomyelin which was released into the medium at 37 degrees C. Release of truncated sphingomyelin was inhibited by low temperature (15 degrees C) but not by the fungal metabolite brefeldin A which, however, arrests protein export from the parasite. While membranes of mammalian cells, including the plasma membrane of non-infected erythrocytes, are impermeable to truncated sphingomyelin, the membrane of infected erythrocytes allowed passage of the molecule in both directions. The results obtained with the unicellular eukaryote used here as an experimental model are discussed in comparison with sphingomyelin synthesis and transport in mammalian cells.

Plasmodium falciparum parasites exit the infected erythrocyte after haemolysis with saponin and streptolysin O

2020 ◽  
Vol 119 (12) ◽  
pp. 4297-4302
Author(s):  
Katharina A. Quadt ◽  
Xanthoula Smyrnakou ◽  
Friedrich Frischknecht ◽  
Guido Böse ◽  
Markus Ganter
Keyword(s):  
Plasmodium Falciparum ◽  
Infected Erythrocyte ◽  
Streptolysin O
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