Published: July 10, 2017
Batinovic S, McHugh E, Chisolm S, Liu B, Dumont L, Charnaud SC, Matthews K, Gilson PR, McMillan PJ, de Koning Ward TF, Dixon MWA, and Tilley L. An Exported Protein-Interacting Complex involved in the trafficking of virulence determinants in Plasmodium-infected erythrocytes. Nat Commun. 2017; 8: 16044. doi: 10.1038/ncomms16044
The malaria parasite, Plasmodium falciparum, displays the P. falciparum erythrocyte membrane protein 1 (PfEMP1) on the surface of infected red blood cells (RBCs). We here examine the physical organization of PfEMP1 trafficking intermediates in infected RBCs and determine interacting partners using an epitope-tagged minimal construct (PfEMP1B). We show that parasitophorous vacuole (PV)-located PfEMP1B interacts with components of the PTEX (Plasmodium Translocon of EXported proteins) as well as a novel protein complex, EPIC (Exported Protein-Interacting Complex). Within the RBC cytoplasm PfEMP1B interacts with components of the Maurer’s clefts and the RBC chaperonin complex. We define the EPIC interactome and, using an inducible knockdown approach, show that depletion of one of its components, the parasitophorous vacuolar protein-1 (PV1), results in altered knob morphology, reduced cell rigidity and decreased binding to CD36. Accordingly, we show that deletion of the Plasmodium berghei homologue of PV1 is associated with attenuation of parasite virulence in vivo.