MAHRP2 is required for tether formation and PfEMP1 trafficking in Plasmodium falciparum infected red blood cells.

ABSTRACT: The ability of the human malaria parasite Plasmodium falciparum to remodel its host red blood cell (RBC) is central to the parasite’s ability to survive within the circulation of its host and cause disease. Following invasion, the parasite exports proteins into the RBC cytoplasm where they remodel the membrane skeleton and alter the cells biophysical properties. Many of the exported proteins are trafficked through parasite derived structures called Maurer’s clefts in the cytoplasm of the RBC. These clefts act as an intermediate compartment for proteins en route to the RBC membrane such as the major virulence protein, Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1). From the Maurer’s clefts, PfEMP1 is delivered to the RBC membrane through a poorly understood process, which is thought to combine physical tethering of the Maurer’s clefts to the membrane and vesicle mediated trafficking. A tube-like structure called the tether can be seen by electron-tomography connecting the Maurer’s clefts to the RBC membrane. To date, the function and formation of these tether structures are unknown, with only one protein, the Membrane Associated Histidine Rich Protein 2 (MAHRP2) known to locate at these structures. In this study, we show that deletion of MAHRP2 ablates tether formation, affects Maurer’s cleft immobilisation at the RBC membrane, resulting in a significant reduction in PfEMP1 trafficking to the membrane and the parasite’s ability to cytoadhere. Lastly, we show that deletion of MAHRP2 leads to global impacts in PTP2 related vesicle formation and a reduction in J-dot chaperone components.

INSTRUMENT(S):

ORGANISM(S): Plasmodium Falciparum (isolate 3d7)

TISSUE(S): Blood Cell, Blood

DISEASE(S): Plasmodium Falciparum Malaria

SUBMITTER: Laura Dagley  

LAB HEAD: Matthew W A Dixon

PROVIDER: PXD065129 | Pride | 2026-06-26

REPOSITORIES: Pride