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 searching approach of the Plasmodium Genomics Resources (www.plasmodb.org), 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 show 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.
Highlights
Infection of the host erythrocyte by the malaria parasite Plasmodium spp. is a crucial event in the pathobiology of this pathogen
The apicoplast and the micronemes are essential to parasite survival
In order to identify putative PL translocases, we used three search criteria available in the Plasmodium Genomics Resource database: (i) Function prediction as determined by EC number and GO term, (ii) transcriptomics data and (iii) protein features and prop erties. This search identified a single exon gene encoding for a putative PL scramblase of approx. 33 kDa, hereafter referred to as PfPLSCR (Fig. 1A), which is predicted to be highly upregulated in late schizont stages (40−48 h post invasion) and to associate with the plasma membrane
Summary
Infection of the host erythrocyte by the malaria parasite Plasmodium spp. is a crucial event in the pathobiology of this pathogen. The asexual, intra-erythrocytic proliferation of Plasmodium spp. is accompanied by a high demand of lipids These lipids are required to build membranes for daughter cell and organelle neogenesis, promote the expansion of the parasitophorous vacuole (PV) in which the parasite resides and develops, and to generate a parasite-derived exomembrane system involved in parasite virulence and nutrient uptake (reviewed in [1,2]). Phosphoinositides have been implicated in merozoite development [4], haemoglobin digestion [5], microneme secretion [6] and apicoplast biogenesis in Plasmodium spp. and its apicomplexan relative Toxoplasma gondii [7,8] Another impor tant lipid messenger, phosphatidic acid, has been linked to micro neme exocytosis [9] and host cell egress in Toxoplasma gondii [10]. In vestigations into the roles played by lipids and their interacting proteins and regulators are increasingly seen as an attractive avenue to explore and to identify novel antimalarial and antiparasitic drug targets
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