Interactions ofPlasmodium falciparumETRAMP14.1 with PfEMP1, translocon components and other ETRAMP members at the interface of host-parasite

Abstract

AbstractThe Early Transcribed Membrane Proteins (ETRAMPs) belong to a multigene family which are conserved, are specific toPlasmodiumspecies, 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 inPlasmodium falciparum. In this study, we report the potential interacting partners ofPfETRAMP14.1 by using immunoprecipitation (IP) LC-MS/MS as well as protein-interaction network reconstructed onin vivoarray analyses of severe malaria inflicted patients from malaria endemic Indian regions. We findPfETRAMP14.1 to be the most highly transcribed gene in severe infection. Our studies with western blot analysis and Immuno-flurorescence show thatPfETRAMP14.1 is expressed at PVM during all the intraerythrocytic stages ofP.falciparumwith maximum expression at early trophozoite stage. Further, our results reveal interactions of ETRAMP14.1 withPlasmodium falciparumerythrocyte 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.