title: Plasmodium falciparum STEVOR phosphorylation regulates host erythrocyte deformability enabling malaria parasite transmission.
abstract: 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.
authors.affiliation: INSERM U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche (UMR) 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratoire d'Excellence GR-Ex, Paris, France;
authors.forename: Bernina
authors.initials: B
authors.lastname: Naissant
authors.affiliation: INSERM U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche (UMR) 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratoire d'Excellence GR-Ex, Paris, France;
authors.forename: Florian
authors.initials: F
authors.lastname: Dupuy
authors.affiliation: INSERM U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche (UMR) 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratoire d'Excellence GR-Ex, Paris, France;
authors.forename: Yoann
authors.initials: Y
authors.lastname: Duffier
authors.affiliation: INSERM U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche (UMR) 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratoire d'Excellence GR-Ex, Paris, France;
authors.forename: Audrey
authors.initials: A
authors.lastname: Lorthiois
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratoire d'Excellence GR-Ex, Paris, France; HRA Pharma, Paris, France;
authors.forename: Julien
authors.initials: J
authors.lastname: Duez
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany;
authors.forename: Judith
authors.initials: J
authors.lastname: Scholz
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratoire d'Excellence GR-Ex, Paris, France;
authors.forename: Pierre
authors.initials: P
authors.lastname: Buffet
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratoire d'Excellence GR-Ex, Paris, France; Institut de Recherche Pour le Développement UMR216, Paris, France; and.
authors.forename: Anais
authors.initials: A
authors.lastname: Merckx
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany;
authors.forename: Anna
authors.initials: A
authors.lastname: Bachmann
authors.affiliation: INSERM U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche (UMR) 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratoire d'Excellence GR-Ex, Paris, France; Genetic and Genomic of Insect Vector Unit, Institut Pasteur, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lavazec
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000378:metabolism*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004907:Erythrocyte Deformability; D006790:Host-Parasite Interactions; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000469:parasitology* / Q000635:transmission*; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C474556:STEVOR antigen, Plasmodium falciparum; D017868:Cyclic AMP-Dependent Protein Kinases