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

Mol Biochem Parasitol. 2021 May:243:111374. doi: 10.1016/j.molbiopara.2021.111374. Epub 2021 May 8.

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.

Keywords: Gametocytes; Invasion; Liposomes; Malaria; Phospholipid scramblase; Plasmodium falciparum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apicomplexa
  • Conserved Sequence
  • Erythrocytes / parasitology
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Liposomes / chemistry
  • Liposomes / metabolism
  • Microorganisms, Genetically-Modified
  • Phospholipid Transfer Proteins / genetics*
  • Phospholipid Transfer Proteins / isolation & purification
  • Phospholipid Transfer Proteins / metabolism
  • Plasmodium falciparum / enzymology*
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / pathogenicity
  • Protozoan Proteins / genetics*
  • Protozoan Proteins / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism

Substances

  • Liposomes
  • PLSCR1 protein, human
  • Phospholipid Transfer Proteins
  • Protozoan Proteins
  • Recombinant Proteins