ArticlePLoS pathogens2022
A positive feedback loop mediates crosstalk between calcium, cyclic nucleotide and lipid signalling in calcium-induced Toxoplasma gondii egress.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Phosphatidylinositol-4-phosphate signaling regulates dense granule biogenesis and maturation in Toxoplasma gondii.PLoS pathogens · 2026Article
- Review
- Unveiling the impact of cGMP-dependent protein kinase of Neospora caninum on calcium fluxes and egress functions through quantitative phosphoproteome analysis.Communications biology · 2025Article
- Finding the brakes on the Toxoplasma life cycle.Trends in parasitology · 2025Article
- Phospho-relay feedback loops control egress vs. intracellular development in Toxoplasma gondii.Cell reports · 2025Article
- Proteomic approaches for protein kinase substrate identification in Apicomplexa.Molecular and biochemical parasitology · 2024Review
- SPARK regulates AGC kinases central to theeLife · 2024Article
- The Cryptosporidium signaling kinase CDPK5 plays an important role in male gametogenesis and parasite virulence.Cell reports · 2024Article
- SPARK regulates AGC kinases central to thebioRxiv : the preprint server for biology · 2024Article
- Review
- Detecting and dissecting signaling crosstalk via the multilayer network integration of signaling and regulatory interactions.Nucleic acids research · 2024Article
- Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulates microneme exocytosis ineLife · 2023Article
- Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulates microneme exocytosis inbioRxiv : the preprint server for biology · 2023Article
- Regulation of phosphoinositide metabolism in Apicomplexan parasites.Frontiers in cell and developmental biology · 2023Review
- Article
- Temporal and thermal profiling of theeLife · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Fundamental processes that govern the lytic cycle of the intracellular parasite Toxoplasma gondii are regulated by several signalling pathways. However, how these pathways are connected remains largely unknown. Here, we compare the phospho-signalling networks during Toxoplasma egress from its host cell by artificially raising cGMP or calcium levels. We show that both egress inducers trigger indistinguishable signalling responses and provide evidence for a positive feedback loop linking calcium and cyclic nucleotide signalling. Using WT and conditional knockout parasites of the non-essential calcium-dependent protein kinase 3 (CDPK3), which display a delay in calcium inonophore-mediated egress, we explore changes in phosphorylation and lipid signalling in sub-minute timecourses after inducing Ca2+ release. These studies indicate that cAMP and lipid metabolism are central to the feedback loop, which is partly dependent on CDPK3 and allows the parasite to respond faster to inducers of egress. Biochemical analysis of 4 phosphodiesterases (PDEs) identified in our phosphoproteomes establishes PDE2 as a cAMP-specific PDE which regulates Ca2+ induced egress in a CDPK3-independent manner. The other PDEs display dual hydrolytic activity and play no role in Ca2+ induced egress. In summary, we uncover a positive feedback loop that enhances signalling during egress, thereby linking several signalling pathways.
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Registered trials
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.