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Cited by 18Malaria Research and ControlLipid metabolism and biosynthesisCancer, Lipids, and Metabolism

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A choline-releasing glycerophosphodiesterase essential for phosphatidylcholine biosynthesis and blood stage development in the malaria parasite

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Ramaprasad, Abhinay, Burda, Paul-Christian, Calvani, Enrica, Sait, Aaron J, Palma-Duran, Susana Alejandra, Withers-Martinez, Chrislaine, Hackett, Fiona, Macrae, James, Collinson, Lucy, Gilberger, Tim Wolf, Blackman, Michael J·2022·eLife
DOI 10.7554/elife.82207PMC PMC9886279

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Abstract

The malaria parasite Plasmodium falciparum synthesizes significant amounts of phospholipids to meet the demands of replication within red blood cells. De novo phosphatidylcholine (PC) biosynthesis via the Kennedy pathway is essential, requiring choline that is primarily sourced from host serum lysophosphatidylcholine (lysoPC). LysoPC also acts as an environmental sensor to regulate parasite sexual differentiation. Despite these critical roles for host lysoPC, the enzyme(s) involved in its breakdown to free choline for PC synthesis are unknown. Here, we show that a parasite glycerophosphodiesterase (PfGDPD) is indispensable for blood stage parasite proliferation. Exogenous choline rescues growth of PfGDPD-null parasites, directly linking PfGDPD function to choline incorporation. Genetic ablation of PfGDPD reduces choline uptake from lysoPC, resulting in depletion of several PC species in the parasite, whilst purified PfGDPD releases choline from glycerophosphocholine in vitro. Our results identify PfGDPD as a choline-releasing glycerophosphodiesterase that mediates a critical step in PC biosynthesis and parasite survival.

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Metadata

Authors
Ramaprasad, A., Burda, P.-C., Calvani, E., Sait, A. J., Palma-Duran, S. A., Withers-Martinez, C., Hackett, F., Macrae, J., Collinson, L., Gilberger, T. W., & Blackman, M. J.
Affiliations
  • The Francis Crick Institute (GB)
  • Universität Hamburg (DE)
  • Malaria Biochemistry Laboratory, The Francis Crick Institute
Corresponding author
  • Gilberger, Tim Wolf
  • Blackman, Michael J
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2022-12-28
Volume
11
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.82207
PMC
PMC9886279
OpenAlex
W4313237556
Cited by
18
References
1
Citations by year
2026: 2 · 2025: 5 · 2024: 9 · 2023: 1 · 2022: 1
FWCI
3.53
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • H2020 Marie Skłodowska-Curie Actions (751865)
  • Wellcome Trust (20318/A/20/Z, CC2129, ISSF2)
  • Cancer Research UK (CC2129)
  • Medical Research Council (CC2129)
  • Deutsche Forschungsgemeinschaft (414222880)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
glycerophosphodiesterase, phosphatidylcholine synthesis, choline release, lysophosphatidylcholine, Kennedy pathway, Plasmodium, Plasmodium falciparum, blood stage development, host-parasite interactions, choline uptake, phospholipid metabolism, sexual differentiation
MeSH terms
Animals, Choline, Erythrocytes, Glycerylphosphorylcholine, Malaria, Parasites, Phosphoric Diester Hydrolases, Plasmodium falciparum, Protozoan Proteins, Malaria, Falciparum

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