Proteomic and Genetic Analyses Demonstrate that Plasmodium berghei Blood Stages Export a Large and Diverse Repertoire of Proteins
| العنوان: | Proteomic and Genetic Analyses Demonstrate that Plasmodium berghei Blood Stages Export a Large and Diverse Repertoire of Proteins |
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| المؤلفون: | Clemens H. M. Kocken, Alan W. Thomas, Jannik Fonager, Onny Klop, Blandine Franke-Fayard, Roberta Spaccapelo, Jan A. Hiss, Thomas D. Otto, Matthew Berriman, Erica M. Pasini, Matthias Mann, Joanna A. M. Braks, Elena Aime, Chris J. Janse |
| المصدر: | Molecular & Cellular Proteomics; Vol 12 Molecular and Cellular Proteomics, 12(2), 426-448 MOLECULAR & CELLULAR PROTEOMICS Molecular & Cellular Proteomics : MCP |
| بيانات النشر: | Elsevier BV, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | CD36 Antigens, SELECTION, Erythrocytes, Proteome, Plasmodium berghei, Protozoan Proteins, genetic analysis, Proteomics, Biochemistry, Analytical Chemistry, Mice, Genes, Reporter, Tandem Mass Spectrometry, FALCIPARUM-INFECTED ERYTHROCYTES, RODENT MALARIA PARASITE, Luciferases, CEREBRAL MALARIA, 0303 health sciences, biology, 3. Good health, Transport protein, Cell biology, MAURERS CLEFTS, Protein Transport, Host cell cytoplasm, Female, EXPRESSION, Transgene, Green Fluorescent Proteins, Schizonts, Transfection, Host-Parasite Interactions, 03 medical and health sciences, parasitic diseases, genetic analysis, Plasmodium berghei, FALCIPARUM-INFECTED ERYTHROCYTES, RODENT MALARIA PARASITE, HOST ERYTHROCYTE, MULTIGENE FAMILY, CEREBRAL MALARIA, MAURERS CLEFTS, LIFE-CYCLE, EXPRESSION, VIRULENCE, SELECTION, Animals, HOST ERYTHROCYTE, Trophozoites, MULTIGENE FAMILY, Molecular Biology, 030304 developmental biology, 030306 microbiology, Research, Plasmodium falciparum, biology.organism_classification, LIFE-CYCLE, Malaria, Cytoplasm, Mutation, VIRULENCE |
| الوصف: | Malaria parasites actively remodel the infected red blood cell (irbc) by exporting proteins into the host cell cytoplasm. The human parasite Plasmodium falciparum exports particularly large numbers of proteins, including proteins that establish a vesicular network allowing the trafficking of proteins onto the surface of irbcs that are responsible for tissue sequestration. Like P. falciparum, the rodent parasite P. berghei ANKA sequesters via irbc interactions with the host receptor CD36. We have applied proteomic, genomic, and reverse-genetic approaches to identify P. berghei proteins potentially involved in the transport of proteins to the irbc surface. A comparative proteomics analysis of P. berghei non-sequestering and sequestering parasites was used to determine changes in the irbc membrane associated with sequestration. Subsequent tagging experiments identified 13 proteins (Plasmodium export element (PEXEL)-positive as well as PEXEL-negative) that are exported into the irbc cytoplasm and have distinct localization patterns: a dispersed and/or patchy distribution, a punctate vesicle-like pattern in the cytoplasm, or a distinct location at the irbc membrane. Members of the PEXEL-negative BIR and PEXEL-positive Pb-fam-3 show a dispersed localization in the irbc cytoplasm, but not at the irbc surface. Two of the identified exported proteins are transported to the irbc membrane and were named erythrocyte membrane associated proteins. EMAP1 is a member of the PEXEL-negative Pb-fam-1 family, and EMAP2 is a PEXEL-positive protein encoded by a single copy gene; neither protein plays a direct role in sequestration. Our observations clearly indicate that P. berghei traffics a diverse range of proteins to different cellular locations via mechanisms that are analogous to those employed by P. falciparum. This information can be exploited to generate transgenic humanized rodent P. berghei parasites expressing chimeric P. berghei/P. falciparum proteins on the surface of rodent irbc, thereby opening new avenues for in vivo screening adjunct therapies that block sequestration. Molecular & Cellular Proteomics 12: 10.1074/mcp.M112.021238, 426-448, 2013. |
| وصف الملف: | application/pdf |
| تدمد: | 1535-9476 |
| DOI: | 10.1074/mcp.m112.021238 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6ad669db70000b30716ef8920f580dcc https://doi.org/10.1074/mcp.m112.021238 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6ad669db70000b30716ef8920f580dcc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15359476 |
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| DOI: | 10.1074/mcp.m112.021238 |