Evidence map›Paper›PMID 39903669›Full record

ArticleCell reports2025

Phospho-relay feedback loops control egress vs. intracellular development in Toxoplasma gondii.

Ja E Claywell, Yong Fu, L David Sibley

Abstract read
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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

3 authors.

Ja E ClaywellDepartment of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Yong FuDepartment of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
L David SibleyDepartment of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA. Electronic address: sibley@wustl.edu.

Funding

Regulation of host cell egress by Toxoplasma gondiiR01AI162749 · NIAID · WASHINGTON UNIVERSITY · PI SIBLEY, L. DAVID · 2022 to 2025
$3.1M
NIAID NIH HHS R01 AI162749
6 · The paper itself

Abstract

The intracellular parasite Toxoplasma gondii alternates between a motile invasive and a quiescent intracellular replicative form, yet how these transitions are regulated is unknown. A positive feedback loop involving protein kinase G (PKG) and calcium-dependent PKs (CDPKs) controls motility, invasion, and egress by Toxoplasma gondii, while PKA isoform c1 (PKAc1) counteracts this pathway. Shortly after invasion, PKAc1 is activated by cyclic AMP (cAMP) produced by adenylate cyclases, leading to the suppression of the PKG/CDPK pathway. PKAc1 further activates phosphodiesterase 2, which selectively consumes cAMP, thus forming a negative feedback loop, causing transient activation of PKAc1. Perturbation of cyclic GMP (cGMP) vs. calcium demonstrates that PKAc1 acts on targets between guanylate cyclase and calcium release. The combined activation of PKG/CDPKs and inhibition by PKAc1, controlled by a transient negative feedback loop, ensures that the parasite is responsive to environmental signals needed to activate motility while also ensuring periods of long-term stable intracellular growth.

Indexed as

Feedback, PhysiologicalToxoplasmaAnimalsCalciumCyclic AMPCyclic GMPCyclic GMP-Dependent Protein KinasesHumansProtozoan ProteinsSignal TransductionCalciumCyclic AMPCyclic GMPCyclic GMP-Dependent Protein KinasesProtozoan ProteinscalciumCP: MicrobiologyCP: Molecular biologyhomeostasisphosphodiesterasephosphorylationprotein kinase Asignaling

Identifiers

PMID39903669
PMCPMC11922314

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.