CoChat
Sign Up
PreprintCited by 1Malaria Research and ControlLipid metabolism and biosynthesisCancer, Lipids, and Metabolism

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

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

Open access
Ramaprasad, Abhinay, Burda, Paul-Christian, Calvani, Enrica, Sait, Aaron, Palma-Duran, Susana Alejandra, Withers-Martinez, Chrislaine, Hackett, Fiona, MacRae, James, Collinson, Lucy, Gilberger, Tim-Wolf, Blackman, Michael J·2022·bioRxiv (Cold Spring Harbor Laboratory)
DOI 10.1101/2022.06.14.496138

Preprint — published as 10.7554/elife.82207 · Paper page

Open this paper in CoChat — free accountOpen PDF

Abstract

Summary: 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. Loss 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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2022.06.14.496138

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 72

  1. 10.1006/jmbi.1994.1052 · DOI
  2. 10.1002/jcc.540150503 · DOI
  3. 10.1016/j.vetpar.2014.05.023 · DOI
  4. 10.1128/AAC.47.8.2590-2597.2003 · DOI
  5. 10.1128/AAC.29.5.814 · DOI
  6. 10.1016/0014-5793(86)80690-1 · DOI
  7. 10.1016/0005-2760(89)90310-x · DOI
  8. 10.1016/0006-2952(85)90390-9 · DOI
  9. 10.1111/j.1365-313X.2011.04693.x · DOI
  10. 10.1182/blood-2004-03-1084 · DOI
  11. 10.1038/nmeth.4223 · DOI
  12. 10.1073/pnas.1301251110 · DOI
  13. 10.12688/wellcomeopenres.14645.4 · DOI
  14. 10.1016/j.cell.2017.10.020 · DOI
  15. 10.1016/j.celrep.2020.107817 · DOI
  16. 10.1093/bioinformatics/btp348 · DOI
  17. 10.1194/jlr.M400079-JLR200 · DOI
  18. 10.1111/mmi.12206 · DOI
  19. 10.1016/j.febslet.2015.03.003 · DOI
  20. 10.1021/ac2021823 · DOI
  21. 10.1038/s41564-020-0702-4 · DOI
  22. 10.1016/j.molbiopara.2012.09.004 · DOI
  23. 10.1371/journal.pone.0221595 · DOI
  24. 10.1186/1471-2105-5-113 · DOI
  25. 10.1074/jbc.M507700200 · DOI
  26. 10.1016/S0166-6851(99)00209-1 · DOI
  27. 10.1016/j.bbalip.2012.08.009 · DOI
  28. 10.1038/nbt.2925 · DOI
  29. 10.1093/oxfordjournals.pcp.a077533 · DOI
  30. 10.1074/jbc.M111.268946 · DOI
  31. 10.1016/j.vetpar.2015.12.024 · DOI
  32. 10.1126/science.aat9689 · DOI
  33. 10.1016/j.chom.2015.08.003 · DOI
  34. 10.1101/2022.01.18.476397 · DOI
  35. 10.1371/journal.ppat.0010029 · DOI
  36. 10.1093/nar/gkm977 · DOI
  37. 10.1038/srep21800 · DOI
  38. 10.1093/bioinformatics/btu031 · DOI
  39. 10.1038/s41598-017-03984-3 · DOI
  40. 10.1093/nar/gkab301 · DOI
  41. 10.1016/j.ttbdis.2019.01.004 · DOI
  42. 10.1186/s12860-014-0043-3 · DOI
  43. 10.1073/pnas.1216457110 · DOI
  44. 10.1104/pp.125.1.423 · DOI
  45. 10.1038/srep20995 · DOI
  46. 10.1242/jcs.00988 · DOI
  47. 10.1128/mBio.00905-18 · DOI
  48. 10.1073/pnas.0307742101 · DOI
  49. 10.1002/prot.21079 · DOI
  50. 10.1128/AAC.00443-06 · DOI
  51. 10.1128/EC.00004-14 · DOI
  52. 10.1038/nbt.1754 · DOI · Paper page
  53. 10.1111/j.1432-1033.1995.tb20646.x · DOI
  54. 10.1038/nmeth.2089 · DOI · Paper page
  55. 10.1038/ismej.2015.172 · DOI
  56. 10.1016/j.phytochem.2015.05.021 · DOI
  57. 10.1038/srep33189 · DOI
  58. 10.1002/prot.21921 · DOI
  59. 10.1007/s11745-000-0656-1 · DOI
  60. 10.1093/bioinformatics/btu033 · DOI · Paper page
  61. 10.1073/pnas.1117654109 · DOI
  62. 10.1371/journal.pone.0157873 · DOI
  63. 10.1002/jssc.201700171 · DOI
  64. 10.1126/science.781840 · DOI
  65. 10.1074/jbc.M112.381723 · DOI
  66. 10.1074/jbc.M113.474189 · DOI
  67. 10.1093/nar/gkab1061 · DOI · Paper page
  68. 10.1016/0005-2760(84)90088-2 · DOI
  69. 10.1016/j.molbiopara.2003.08.017 · DOI
  70. 10.1194/jlr.M085589 · DOI
  71. 10.1074/jbc.M804360200 · DOI
  72. 10.1126/science.aap7847 · DOI

Metadata

Authors
Ramaprasad, A., Burda, P.-C., Calvani, E., Sait, A., 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)
Corresponding author
  • Gilberger, Tim-Wolf
  • Blackman, Michael J
ORCID
Venue
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Published
2022-06-14
DOI
10.1101/2022.06.14.496138
OpenAlex
W4282931287
Cited by
1
References
1
Citations by year
2025: 1
Type
posted content
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Desy publication database (The Deutsches Elektronen-Synchrotron) (submittedVersion, cc-by)
  • Figshare (submittedVersion, cc-by)
  • The Francis Crick Institute (cc-by)
Funders
  • Wellcome Trust (ISSF2, 751865, 20318/A/20/Z, FC001043)
  • Francis Crick Institute (FC001043)
  • International Seafood Sustainability Foundation
  • Cancer Research UK (FC001043)
  • Deutsche Forschungsgemeinschaft (414222880)
  • Medical Research Council (FC001043)
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
Plasmodium falciparum, glycerophosphodiesterase, phosphatidylcholine synthesis, choline release, lysophosphatidylcholine, Kennedy pathway, blood stage development, host-parasite interactions, choline uptake, phospholipid metabolism, parasite proliferation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review