Interactions of Plasmodium falciparum ETRAMP14.1 with PfEMP1, translocon components and other ETRAMP members at the interface of host-parasite

Abstract

The Early Transcribed Membrane Proteins (ETRAMPs) belong to a multigene family which are conserved, are specific to Plasmodium species, and abundantly present in parasitophorous vacuolar membrane (PVM). The functions of the members of this family are poorly understood. PfETRAMP14.1 (PF3D7_1401400) is a member of this family, present only in Plasmodium falciparum. In this study, we report the potential interacting partners of PfETRAMP14.1 by using immunoprecipitation (IP) LC-MS/MS as well as protein-interaction network reconstructed on in vivo array analyses of severe malaria inflicted patients from malaria endemic Indian regions. We find PfETRAMP14.1 to be the most highly transcribed gene in severe infection. Our studies with western blot analysis and Immuno-flurorescence show that PfETRAMP14.1 is expressed at PVM during all the intraerythrocytic stages of P.falciparum with maximum expression at early trophozoite stage. Further, our results reveal interactions of ETRAMP14.1 with Plasmodium falciparum erythrocyte membrane protein 1(PfEMP1), thioredoxin (TRX2), export protein 2 (EXP2), heat shock protein 70-1 (Hsp70-1) and some of the ETRAMP family members. We propose that ETRAMP14.1 helps trafficking of PfEMP1 to the host RBC surface in conjunction with translocon machinery and the chaperone HSP 70-1.