1. Microbiology and Infectious Disease

The Plasmodium falciparum rhoptry protein RhopH3 plays essential roles in host cell invasion and nutrient uptake

  1. Emma S Sherling
  2. Ellen Knuepfer
  3. Joseph A Brzostowski
  4. Louis H Miller
  5. Michael J Blackman  Is a corresponding author
  6. Christiaan van Ooij  Is a corresponding author
  1. The Francis Crick Institute, United Kingdom
  2. National Institute of Allergy and Infectious Disease, National Institute of Health, United States
  3. London School of Hygiene and Tropical Medicine, United Kingdom
https://doi.org/10.7554/eLife.23239
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  1. Emma S Sherling
  2. Ellen Knuepfer
  3. Joseph A Brzostowski
  4. Louis H Miller
  5. Michael J Blackman
  6. Christiaan van Ooij
(2017)
The Plasmodium falciparum rhoptry protein RhopH3 plays essential roles in host cell invasion and nutrient uptake
eLife 6:e23239.
https://doi.org/10.7554/eLife.23239
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Abstract

Merozoites of the protozoan parasite responsible for the most virulent form of malaria, Plasmodium falciparum, invade erythrocytes. Invasion involves discharge of rhoptries, specialized secretory organelles. Once intracellular, parasites induce increased nutrient uptake by generating new permeability pathways (NPP) including a Plasmodium surface anion channel (PSAC). RhopH1/Clag3, one member of the three-protein RhopH complex, is important for PSAC/NPP activity. However, the roles of the other members of the RhopH complex in PSAC/NPP establishment are unknown and it is unclear whether any of the RhopH proteins play a role in invasion. Here we demonstrate that RhopH3, the smallest component of the complex, is essential for parasite survival. Conditional truncation of RhopH3 substantially reduces invasive capacity. Those mutant parasites that do invade are defective in nutrient import and die. Our results identify a dual role for RhopH3 that links erythrocyte invasion to formation of the PSAC/NPP essential for parasite survival within host erythrocytes.

Article and author information

Author details

  1. Emma S Sherling

    1. The Francis Crick Institute, London, United Kingdom
    2. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institute of Health, Rockville, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Ellen Knuepfer

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  3. Joseph A Brzostowski

    Laboratory of Immunogenetics Imaging Facility, National Institute of Allergy and Infectious Disease, National Institute of Health, Rockville, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Louis H Miller

    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institute of Health, Rockville, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Michael J Blackman

    1. The Francis Crick Institute, London, United Kingdom
    2. Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom
    For correspondence
    Mike.Blackman@crick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

  6. Christiaan van Ooij

    The Francis Crick Institute, London, United Kingdom
    For correspondence
    Christiaan.vanOoij@crick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6099-6183

Funding

Wellcome (FC001043)

  • Michael J Blackman

Cancer Research UK (FC001043)

  • Michael J Blackman

National Institutes of Health

  • Louis H Miller

Medical Research Council (FC001043)

  • Michael J Blackman

Wellcome (095836/Z/11/Z)

  • Christiaan van Ooij

Wellcome (013459/Z/14/Z)

  • Emma S Sherling

National Institutes of Health

  • Emma S Sherling

National Institutes of Health

  • Joseph A Brzostowski

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Dominique Soldati-Favre, University of Geneva, Switzerland

Version history

  1. Received: November 12, 2016
  2. Accepted: February 26, 2017
  3. Accepted Manuscript published: March 2, 2017 (version 1)
  4. Accepted Manuscript updated: March 3, 2017 (version 2)
  5. Version of Record published: March 24, 2017 (version 3)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Emma S Sherling
  2. Ellen Knuepfer
  3. Joseph A Brzostowski
  4. Louis H Miller
  5. Michael J Blackman
  6. Christiaan van Ooij
(2017)
The Plasmodium falciparum rhoptry protein RhopH3 plays essential roles in host cell invasion and nutrient uptake
eLife 6:e23239.
https://doi.org/10.7554/eLife.23239

Share this article

https://doi.org/10.7554/eLife.23239

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Further reading

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    Research Article Updated

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