Erythrocyte membrane protein 3 (EMAP3) is exposed on the surface of thePlasmodium bergheiinfected red blood cell

Abstract

The human malaria parasitePlasmodium falciparuminvades red blood cells (RBC) and exports parasite proteins to transform the host cell for its survival. These exported proteins facilitate uptake of nutrients and cytoadherence of the infected RBC (iRBC) to endothelial cells of small blood vessels, thus protecting the iRBC from splenic clearance. The parasite protein PfEMP1 and the host protein CD36 play a major role inP. falciparumiRBC cytoadherence. The murine parasitePlasmodium bergheiis a widely used experimental model that combines high genetic tractability with access toin vivostudies.P. berghei iRBC also sequesters in small blood vessels, mediated by binding to CD36. However, the parasite proteins binding to CD36 are unknown and only very few parasite proteins, including EMAP1 and EMAP2, have been identified that are present at the iRBC membrane. We have identified a new protein named EMAP3 and demonstrated its export to the iRBC membrane where it interacts with EMAP1, with only EMAP3 exposed on the outer surface of the iRBC. Parasites lacking EMAP3 display no significant reduction in growth or sequestration, indicating that EMAP3 is not the major CD36-binding protein. The outer-surface location of EMAP3 offers a new scaffold for displayingP. falciparumproteins on the surface of theP. bergheiiRBC, providing a platform to screenin vivoputative inhibitors ofP. falciparumcytoadherence.