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Proteomic and Genetic Analyses Demonstrate that Plasmodium berghei Blood Stages Export a Large and Diverse Repertoire of Proteins

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 protein...

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Autores principales: Pasini, Erica M., Braks, Joanna A., Fonager, Jannik, Klop, Onny, Aime, Elena, Spaccapelo, Roberta, Otto, Thomas D., Berriman, Matt, Hiss, Jan A., Thomas, Alan W., Mann, Matthias, Janse, Chris J., Kocken, Clemens H. M., Franke-Fayard, Blandine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Biochemistry and Molecular Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567864/
https://www.ncbi.nlm.nih.gov/pubmed/23197789
http://dx.doi.org/10.1074/mcp.M112.021238
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author Pasini, Erica M.
Braks, Joanna A.
Fonager, Jannik
Klop, Onny
Aime, Elena
Spaccapelo, Roberta
Otto, Thomas D.
Berriman, Matt
Hiss, Jan A.
Thomas, Alan W.
Mann, Matthias
Janse, Chris J.
Kocken, Clemens H. M.
Franke-Fayard, Blandine
author_facet Pasini, Erica M.
Braks, Joanna A.
Fonager, Jannik
Klop, Onny
Aime, Elena
Spaccapelo, Roberta
Otto, Thomas D.
Berriman, Matt
Hiss, Jan A.
Thomas, Alan W.
Mann, Matthias
Janse, Chris J.
Kocken, Clemens H. M.
Franke-Fayard, Blandine
author_sort Pasini, Erica M.
collection PubMed
description 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.
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spelling pubmed-35678642013-02-11 Proteomic and Genetic Analyses Demonstrate that Plasmodium berghei Blood Stages Export a Large and Diverse Repertoire of Proteins Pasini, Erica M. Braks, Joanna A. Fonager, Jannik Klop, Onny Aime, Elena Spaccapelo, Roberta Otto, Thomas D. Berriman, Matt Hiss, Jan A. Thomas, Alan W. Mann, Matthias Janse, Chris J. Kocken, Clemens H. M. Franke-Fayard, Blandine Mol Cell Proteomics Research 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. The American Society for Biochemistry and Molecular Biology 2013-02 2012-11-28 /pmc/articles/PMC3567864/ /pubmed/23197789 http://dx.doi.org/10.1074/mcp.M112.021238 Text en © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles
spellingShingle Research
Pasini, Erica M.
Braks, Joanna A.
Fonager, Jannik
Klop, Onny
Aime, Elena
Spaccapelo, Roberta
Otto, Thomas D.
Berriman, Matt
Hiss, Jan A.
Thomas, Alan W.
Mann, Matthias
Janse, Chris J.
Kocken, Clemens H. M.
Franke-Fayard, Blandine
Proteomic and Genetic Analyses Demonstrate that Plasmodium berghei Blood Stages Export a Large and Diverse Repertoire of Proteins
title Proteomic and Genetic Analyses Demonstrate that Plasmodium berghei Blood Stages Export a Large and Diverse Repertoire of Proteins
title_full Proteomic and Genetic Analyses Demonstrate that Plasmodium berghei Blood Stages Export a Large and Diverse Repertoire of Proteins
title_fullStr Proteomic and Genetic Analyses Demonstrate that Plasmodium berghei Blood Stages Export a Large and Diverse Repertoire of Proteins
title_full_unstemmed Proteomic and Genetic Analyses Demonstrate that Plasmodium berghei Blood Stages Export a Large and Diverse Repertoire of Proteins
title_short Proteomic and Genetic Analyses Demonstrate that Plasmodium berghei Blood Stages Export a Large and Diverse Repertoire of Proteins
title_sort proteomic and genetic analyses demonstrate that plasmodium berghei blood stages export a large and diverse repertoire of proteins
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567864/
https://www.ncbi.nlm.nih.gov/pubmed/23197789
http://dx.doi.org/10.1074/mcp.M112.021238
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