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In Vivo Assessment of Rodent Plasmodium Parasitemia and Merozoite Invasion by Flow Cytometry
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Binding of Plasmodium merozoite proteins RON2 and AMA1 triggers commitment to invasion

Prakash Srinivasan1, Wandy L Beatty, Ababacar Diouf

  • 1Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. srinivasanp@niaid.nih.gov

Proceedings of the National Academy of Sciences of the United States of America
|July 27, 2011
PubMed

Insights

Plasmodium merozoite invasion of red blood cells (RBCs) is triggered by the interaction between RON2 and AMA1 proteins. This interaction commits parasites to invasion and identifies RON2 as a potential vaccine candidate.

Area of Science:

  • Malariology
  • Cellular Biology
  • Parasitology

Background:

  • Plasmodium merozoites invade red blood cells (RBCs) through a complex process involving junction formation and parasitophorous vacuole induction.
  • The molecular mechanisms underlying the commitment of Plasmodium merozoites to RBC invasion remain incompletely understood.

Purpose of the Study:

  • To elucidate the molecular events triggering Plasmodium merozoite commitment to RBC invasion.
  • To identify the specific interactions between parasite proteins essential for invasion.
  • To evaluate the potential of identified proteins as vaccine candidates.

Main Methods:

  • Utilized antibodies (Abs) targeting the AMA1 protein's hydrophobic pocket.
  • Employed mutated AMA1 proteins to map the RON2 binding site.
  • Investigated the effects of specific Abs and RON2 peptides on junction and parasitophorous vacuole formation.

Main Results:

  • Identified the binding of RON2 to AMA1's hydrophobic pocket as essential for triggering junction formation.
  • Demonstrated that antibodies specific for the AMA1 pocket block both junction and parasitophorous vacuole formation.
  • Showed that RON2 peptide binding blocks junction formation but not parasitophorous vacuole formation, indicating distinct molecular steps.

Conclusions:

  • The binding of RON2 to AMA1 is the critical step committing Plasmodium merozoites to RBC invasion.
  • Junction formation and parasitophorous vacuole induction are distinct molecularly regulated processes.
  • RON2 represents a promising target for malaria vaccine development.

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