Plasmodium falciparum STEVOR phosphorylation regulates host erythrocyte deformability enabling malaria parasite transmission

Blood. 2016 Jun 16;127(24):e42-53. doi: 10.1182/blood-2016-01-690776. Epub 2016 May 2.


Deformability of Plasmodium falciparum gametocyte-infected erythrocytes (GIEs) allows them to persist for several days in blood circulation and to ensure transmission to mosquitoes. Here, we investigate the mechanism by which the parasite proteins STEVOR (SubTElomeric Variable Open Reading frame) exert changes on GIE deformability. Using the microsphiltration method, immunoprecipitation, and mass spectrometry, we produce evidence that GIE stiffness is dependent on the cytoplasmic domain of STEVOR that interacts with ankyrin complex at the erythrocyte skeleton. Moreover, we show that GIE deformability is regulated by protein kinase A (PKA)-mediated phosphorylation of the STEVOR C-terminal domain at a specific serine residue (S324). Finally, we show that the increase of GIE stiffness induced by sildenafil (Viagra) is dependent on STEVOR phosphorylation status and on another independent mechanism. These data provide new insights into mechanisms by which phosphodiesterase inhibitors may block malaria parasite transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Protozoan / metabolism*
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Erythrocyte Deformability*
  • Host-Parasite Interactions
  • Humans
  • Malaria, Falciparum / blood
  • Malaria, Falciparum / parasitology*
  • Malaria, Falciparum / transmission*
  • Phosphorylation
  • Plasmodium falciparum* / growth & development
  • Plasmodium falciparum* / metabolism
  • Plasmodium falciparum* / pathogenicity
  • Protozoan Proteins / metabolism


  • Antigens, Protozoan
  • Protozoan Proteins
  • STEVOR antigen, Plasmodium falciparum
  • Cyclic AMP-Dependent Protein Kinases