An exported protein-interacting complex involved in the trafficking of virulence determinants in Plasmodium-infected erythrocytes

• Published in: Nature communications 2017-07, Vol.8 (1), p.16044-16044, Article 16044
• Main Authors: Batinovic, Steven, McHugh, Emma, Chisholm, Scott A., Matthews, Kathryn, Liu, Boiyin, Dumont, Laure, Charnaud, Sarah C., Schneider, Molly Parkyn, Gilson, Paul R., de Koning-Ward, Tania F., Dixon, Matthew W. A., Tilley, Leann
• Format: Article
• Language: English
• Subjects: 14/63; 42/109; 631/326/417/1716; 631/80/313/2376; 692/699/255/1629; 82/1; Animals; Carrier Proteins - metabolism; CD36 antigen; Cell Adhesion; Clonal deletion; Cytology; Cytoplasm; Epitopes; Erythrocyte membrane protein 1; Erythrocytes; Exports; Female; Gene Knockdown Techniques; Homology; Host-Pathogen Interactions; Humanities and Social Sciences; Intermediates; Malaria; Membrane proteins; Membrane Proteins - metabolism; Mice, Inbred C57BL; multidisciplinary; Parasitophorous vacuole; Plasmodium berghei - genetics; Plasmodium falciparum; Plasmodium falciparum - metabolism; Plasmodium falciparum - pathogenicity; Protein Transport; Proteins; Protozoan Proteins - metabolism; Rigidity; Science; Science (multidisciplinary); Vector-borne diseases; Virulence
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms16044

The malaria parasite, Plasmodium falciparum , displays the P. falciparum erythrocyte membrane protein 1 ( Pf EMP1) on the surface of infected red blood cells (RBCs). We here examine the physical organization of Pf EMP1 trafficking intermediates in infected RBCs and determine interacting partners using an epitope-tagged minimal construct ( Pf EMP1B). We show that parasitophorous vacuole (PV)-located Pf EMP1B 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 Pf EMP1B 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 P lasmodium berghei homologue of PV1 is associated with attenuation of parasite virulence in vivo . Plasmodium-infected red blood cells export virulence factors, such as Pf EMP1, to the cell surface. Here, the authors identify a protein complex termed EPIC that interacts with Pf EMP1 during export, and they show that knockdown of an EPIC component affects parasite virulence.