Evidence map›Paper›PMID 24594931›Full record

ArticlePLoS biology2014

Phosphoinositide metabolism links cGMP-dependent protein kinase G to essential Ca²⁺ signals at key decision points in the life cycle of malaria parasites.

Mathieu Brochet, Mark O Collins, Terry K Smith, Eloise Thompson, Sarah Sebastian, Katrin Volkmann, Frank Schwach, Lia Chappell, Ana Rita Gomes, Matthew Berriman and 4 more

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
136citing papers in PubMed, 1 pooled it
17.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

136 citing papers in PubMed, 1 synthesis or guideline pooled it, 234 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Molecular mechanisms involved inFrontiers in microbiology · 2026
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  12. Molecular biology of the cell · 2025
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  16. Elevated NADNature communications · 2025
    Article
  17. Review
  18. Article
  19. mBio · 2024
    Article
  20. Orthologs ofMicrobiology spectrum · 2024
    Article

76 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Mathieu BrochetWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Mark O CollinsWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Terry K SmithSchools of Biology and Chemistry, Biomedical Sciences Research Complex, The North Haugh, The University of Saint Andrews, St. Andrews, Fife United Kingdom.
Eloise ThompsonFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Sarah SebastianWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Katrin VolkmannWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Frank SchwachWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Lia ChappellWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Ana Rita GomesWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Matthew BerrimanWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Julian C RaynerWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
David A BakerFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Jyoti ChoudharyWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Oliver BillkerWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Wellcome Sanger Institute · GBLondon School of Hygiene & Tropical Medicine · GBUniversity of St Andrews · GB

Funding

Medical Research Council G0501670Medical Research Council G10000779Wellcome TrustWellcome Trust 079643/Z/06/ZWellcome Trust WT093228Wellcome Trust WT094752Wellcome Trust WT098051
6 · The paper itself

Abstract

Many critical events in the Plasmodium life cycle rely on the controlled release of Ca²⁺ from intracellular stores to activate stage-specific Ca²⁺-dependent protein kinases. Using the motility of Plasmodium berghei ookinetes as a signalling paradigm, we show that the cyclic guanosine monophosphate (cGMP)-dependent protein kinase, PKG, maintains the elevated level of cytosolic Ca²⁺ required for gliding motility. We find that the same PKG-dependent pathway operates upstream of the Ca²⁺ signals that mediate activation of P. berghei gametocytes in the mosquito and egress of Plasmodium falciparum merozoites from infected human erythrocytes. Perturbations of PKG signalling in gliding ookinetes have a marked impact on the phosphoproteome, with a significant enrichment of in vivo regulated sites in multiple pathways including vesicular trafficking and phosphoinositide metabolism. A global analysis of cellular phospholipids demonstrates that in gliding ookinetes PKG controls phosphoinositide biosynthesis, possibly through the subcellular localisation or activity of lipid kinases. Similarly, phosphoinositide metabolism links PKG to egress of P. falciparum merozoites, where inhibition of PKG blocks hydrolysis of phosphatidylinostitol (4,5)-bisphosphate. In the face of an increasing complexity of signalling through multiple Ca²⁺ effectors, PKG emerges as a unifying factor to control multiple cellular Ca²⁺ signals essential for malaria parasite development and transmission.

Indexed as

Calcium SignalingAnimalsCulicidaeCyclic GMP-Dependent Protein KinasesHost-Parasite InteractionsHumansLife Cycle StagesMalariaModels, BiologicalPhosphatidylinositolsPlasmodium falciparumCyclic GMP-Dependent Protein KinasesPhosphatidylinositols

Identifiers

PMID24594931
PMCPMC3942320
OpenAlexW1987368684

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.