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Proteomic analysis of detergent-resistant membrane microdomains in trophozoite blood stage of the human malaria parasite Plasmodium falciparum.
- Source :
-
Molecular & cellular proteomics : MCP [Mol Cell Proteomics] 2013 Dec; Vol. 12 (12), pp. 3948-61. Date of Electronic Publication: 2013 Sep 17. - Publication Year :
- 2013
-
Abstract
- Intracellular pathogens contribute to a significant proportion of infectious diseases worldwide. The successful strategy of evading the immune system by hiding inside host cells is common to all the microorganism classes, which exploit membrane microdomains, enriched in cholesterol and sphingolipids, to invade and colonize the host cell. These assemblies, with distinct biochemical properties, can be isolated by means of flotation in sucrose density gradient centrifugation because they are insoluble in nonionic detergents at low temperature. We analyzed the protein and lipid contents of detergent-resistant membranes from erythrocytes infected by Plasmodium falciparum, the most deadly human malaria parasite. Proteins associated with membrane microdomains of trophic parasite blood stages (trophozoites) include an abundance of chaperones, molecules involved in vesicular trafficking, and enzymes implicated in host hemoglobin degradation. About 60% of the identified proteins contain a predicted localization signal suggesting a role of membrane microdomains in protein sorting/trafficking. To validate our proteomic data, we raised antibodies against six Plasmodium proteins not characterized previously. All the selected candidates were recovered in floating low-density fractions after density gradient centrifugation. The analyzed proteins localized either to internal organelles, such as the mitochondrion and the endoplasmic reticulum, or to exported membrane structures, the parasitophorous vacuole membrane and Maurer's clefts, implicated in targeting parasite proteins to the host erythrocyte cytosol or surface. The relative abundance of cholesterol and phospholipid species varies in gradient fractions containing detergent-resistant membranes, suggesting heterogeneity in the lipid composition of the isolated microdomain population. This study is the first report showing the presence of cholesterol-rich microdomains with distinct properties and subcellular localization in trophic stages of Plasmodium falciparum.
- Subjects :
- Antibodies chemistry
Centrifugation, Density Gradient
Cholesterol chemistry
Cysteine Endopeptidases genetics
Cysteine Endopeptidases metabolism
Detergents chemistry
Erythrocyte Membrane parasitology
Fluorescent Antibody Technique, Indirect
Gene Expression
Host-Parasite Interactions
Humans
Intracellular Membranes chemistry
Membrane Microdomains parasitology
Molecular Chaperones genetics
Molecular Chaperones metabolism
Molecular Sequence Annotation
Phospholipids chemistry
Plasmodium falciparum chemistry
Plasmodium falciparum metabolism
Protein Transport
Proteome metabolism
Protozoan Proteins metabolism
Trophozoites chemistry
Erythrocyte Membrane chemistry
Membrane Microdomains chemistry
Plasmodium falciparum genetics
Proteome genetics
Protozoan Proteins genetics
Trophozoites metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1535-9484
- Volume :
- 12
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Molecular & cellular proteomics : MCP
- Publication Type :
- Academic Journal
- Accession number :
- 24045696
- Full Text :
- https://doi.org/10.1074/mcp.M113.029272