Identification and characterisation of a phospholipid scramblase in the malaria parasite Plasmodium falciparum

Abstract

Recent studies highlight the emerging role of lipids as important messengers in malaria parasite biology. In an attempt to identify interacting proteins and regulators of these dynamic and versatile molecules, we hypothesised the involvement of phospholipid translocases and their substrates in the infection of the host erythrocyte by the malaria parasite Plasmodium spp. Here, using a data base mining approach, we have identified a putative phospholipid (PL) scramblase in P. falciparum (PfPLSCR) that is conserved across the genus and in closely related unicellular algae. By reconstituting recombinant PfPLSCR into liposomes, we demonstrate metal ion dependent PL translocase activity and substrate preference, confirming PfPLSCR as a bona fide scramblase. We confirm that PfPLSCR is expressed during asexual and sexual parasite development, localising to different membranous compartments of the parasite throughout the intra-erythrocytic life cycle. Two different gene knockout approaches, however, suggest that PfPLSCR is not essential for erythrocyte invasion and asexual parasite development, pointing towards a possible role in other stages of the parasite life cycle.

Breakdown in membrane asymmetry regulation leads to monocyte recognition of P. falciparum-infected red blood cells

“…In the light of our findings, it would be interesting for future studies to determine the substrate specificity and cholesterol/Ca 2+ sensitivity of these proteins. A candidate Plasmodium scramblase protein (PF3D7_1022700) has recently been identified and characterised, and could be responsible for energy-independent lipid internalisation to the parasite observed in this study [ 94 [pre-print]].…”

Glycosphingolipid GM3 is localized in both exoplasmic and cytoplasmic leaflets of Plasmodium falciparum malaria parasite plasma membrane

“…However, the molecules responsible for the transbilayer flip-flop of ganglyosides such as GM1 or GM3 have not been identified 51 , 52 . However, some scramblases possess transbilayer moving activity for galactosylceramide and glucosylceramide in mammalian cells 53 and for glycerophospholipids in P. falciparum 54 . Furthermore, in mammalian cells, it was reported that the phosphoethanolamine (PE) analog NBD-PE 55 and phosphotidylserine (PS) analog NBD-PS 56 were translocated from the plasma membrane to the intracellular organelles’ membranes by monomer diffusion when they are exogenously applied to the cell culture medium.…”