A pan-apicomplexan phosphoinositide-binding protein acts in malarial microneme exocytosis

EMBO Rep. 2019 Jun;20(6):e47102. doi: 10.15252/embr.201847102. Epub 2019 May 16.


Invasion of human red blood cells by the malaria parasite Plasmodium falciparum is an essential step in the development of the disease. Consequently, the molecular players involved in host cell invasion represent important targets for inhibitor design and vaccine development. The process of merozoite invasion is a succession of steps underlined by the sequential secretion of the organelles of the apical complex. However, little is known with regard to how their contents are exocytosed. Here, we identify a phosphoinositide-binding protein conserved in apicomplexan parasites and show that it is important for the attachment and subsequent invasion of the erythrocyte by the merozoite. Critically, removing the protein from its site of action by knock sideways preferentially prevents the secretion of certain types of micronemes. Our results therefore provide evidence for a role of phosphoinositide lipids in the malaria invasion process and provide further insight into the secretion of microneme organelle populations, which is potentially applicable to diverse apicomplexan parasites.

Keywords: exocytosis; invasion; malaria; microneme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Conserved Sequence
  • Erythrocytes / parasitology
  • Exocytosis*
  • Humans
  • Life Cycle Stages
  • Phosphatidylinositols / metabolism
  • Plasmodium falciparum / physiology*
  • Pleckstrin Homology Domains
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*


  • Phosphatidylinositols
  • Protozoan Proteins