Spatial and temporal mapping of the PfEMP1 export pathway in Plasmodium falciparum

Authors

  • Paul J. McMillan,

    1. Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Vic., Australia
    2. ARC Centre of Excellence for Coherent X-ray Science, The University of Melbourne, Melbourne, Vic., Australia
    3. Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Vic., Australia
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  • Coralie Millet,

    1. Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Vic., Australia
    2. ARC Centre of Excellence for Coherent X-ray Science, The University of Melbourne, Melbourne, Vic., Australia
    3. Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Vic., Australia
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    • These authors contributed equally.
  • Steven Batinovic,

    1. Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Vic., Australia
    2. ARC Centre of Excellence for Coherent X-ray Science, The University of Melbourne, Melbourne, Vic., Australia
    3. Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Vic., Australia
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    • These authors contributed equally.
  • Mauro Maiorca,

    1. Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Vic., Australia
    2. ARC Centre of Excellence for Coherent X-ray Science, The University of Melbourne, Melbourne, Vic., Australia
    3. Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Vic., Australia
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  • Eric Hanssen,

    1. ARC Centre of Excellence for Coherent X-ray Science, The University of Melbourne, Melbourne, Vic., Australia
    2. Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Vic., Australia
    3. Advanced Microscopy Facility, The University of Melbourne, Melbourne, Vic., Australia
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  • Shannon Kenny,

    1. Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Vic., Australia
    2. ARC Centre of Excellence for Coherent X-ray Science, The University of Melbourne, Melbourne, Vic., Australia
    3. Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Vic., Australia
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  • Rebecca A. Muhle,

    1. Department of Microbiology & Immunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA
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  • Martin Melcher,

    1. Seattle Biomedical Research Institute, Seattle, WA, USA
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  • David A. Fidock,

    1. Department of Microbiology & Immunology, Columbia University Medical Center, New York, NY, USA
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  • Joseph D. Smith,

    1. Seattle Biomedical Research Institute, Seattle, WA, USA
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  • Matthew W. A. Dixon,

    1. Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Vic., Australia
    2. ARC Centre of Excellence for Coherent X-ray Science, The University of Melbourne, Melbourne, Vic., Australia
    3. Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Vic., Australia
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  • Leann Tilley

    Corresponding author
    1. ARC Centre of Excellence for Coherent X-ray Science, The University of Melbourne, Melbourne, Vic., Australia
    2. Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Vic., Australia
    • Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Vic., Australia
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For correspondence. E-mail ltilley@unimelb.edu.au; Tel. (+61) 3 8344 2227; Fax (+61) 3 9348 1421.

Summary

The human malaria parasite, Plasmodium falciparum, modifies the red blood cells (RBCs) that it infects by exporting proteins to the host cell. One key virulence protein, P. falciparum Erythrocyte Membrane Protein-1 (PfEMP1), is trafficked to the surface of the infected RBC, where it mediates adhesion to the vascular endothelium. We have investigated the organization and development of the exomembrane system that is used for PfEMP1 trafficking. Maurer's cleft cisternae are formed early after invasion and proteins are delivered to these (initially mobile) structures in a temporally staggered and spatially segregated manner. Membrane-Associated Histidine-Rich Protein-2(MAHRP2)-containing tether-like structures are generated as early as 4 h post invasion and become attached to Maurer's clefts. The tether/Maurer's cleft complex docks onto the RBC membrane at ∼ 20 h post invasion via a process that is not affected by cytochalasin D treatment. We have examined the trafficking of a GFP chimera of PfEMP1 expressed in transfected parasites. PfEMP1B-GFP accumulates near the parasite surface, within membranous structures exhibiting a defined ultrastructure, before being transferred to pre-formed mobile Maurer's clefts. Endogenous PfEMP1 and PfEMP1B-GFP are associated with Electron-Dense Vesicles that may be responsible for trafficking PfEMP1 from the Maurer's clefts to the RBC membrane.

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