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

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

Author information

1
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;
2
Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratoire d'Excellence GR-Ex, Paris, France; HRA Pharma, Paris, France;
3
Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany;
4
Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratoire d'Excellence GR-Ex, Paris, France;
5
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.
6
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.

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.

PMID:
27136945
DOI:
10.1182/blood-2016-01-690776
[Indexed for MEDLINE]
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