Subcompartmentalisation of proteins in the rhoptries correlates with ordered events of erythrocyte invasion by the blood stage malaria parasite

PLoS One. 2012;7(9):e46160. doi: 10.1371/journal.pone.0046160. Epub 2012 Sep 25.


Host cell infection by apicomplexan parasites plays an essential role in lifecycle progression for these obligate intracellular pathogens. For most species, including the etiological agents of malaria and toxoplasmosis, infection requires active host-cell invasion dependent on formation of a tight junction - the organising interface between parasite and host cell during entry. Formation of this structure is not, however, shared across all Apicomplexa or indeed all parasite lifecycle stages. Here, using an in silico integrative genomic search and endogenous gene-tagging strategy, we sought to characterise proteins that function specifically during junction-dependent invasion, a class of proteins we term invasins to distinguish them from adhesins that function in species specific host-cell recognition. High-definition imaging of tagged Plasmodium falciparum invasins localised proteins to multiple cellular compartments of the blood stage merozoite. This includes several that localise to distinct subcompartments within the rhoptries. While originating from the same organelle, however, each has very different dynamics during invasion. Apical Sushi Protein and Rhoptry Neck protein 2 release early, following the junction, whilst a novel rhoptry protein PFF0645c releases only after invasion is complete. This supports the idea that organisation of proteins within a secretory organelle determines the order and destination of protein secretion and provides a localisation-based classification strategy for predicting invasin function during apicomplexan parasite invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Erythrocytes / parasitology*
  • Fluorescent Antibody Technique
  • Host-Parasite Interactions
  • Humans
  • Malaria / parasitology*
  • Microscopy, Immunoelectron
  • Organelles / metabolism*
  • Organelles / ultrastructure
  • Plasmodium falciparum / metabolism*
  • Plasmodium falciparum / pathogenicity*
  • Protozoan Proteins / metabolism*


  • Protozoan Proteins

Grant support

This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. Funding for the research came from the National Health and Medical Research Council of Australia (NHMRC Project Grant 637340 JB and SAR) and the Human Frontier Science Program (HFSP Young Investigator Program Grant RGY0071/2011 JB). ESZ is supported by an Australian Postgraduate Award (APA); AMG was the recipient of a University of Melbourne Postgraduate Research Scholarship (MRS); FA is supported by a Walter & Eliza Hall Institute Postgraduate Scholarship; DTR is supported by a Pratt Foundation PhD scholarship through the University of Melbourne; LT is supported by a Chancellor’s Postdoctoral Fellowship from the University of Technology, Sydney; CBW is supported by a Senior Research Fellowship from the NHMRC; SAR is supported by an Australian Research Council (ARC) Future Fellowship (FT0990350); TPS is supported by an Australia Fellowship from the NHMRC. JB is supported by an ARC Future Fellowship (FT100100112). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.