ArticlePLoS biology2018
Protein kinase A negatively regulates Ca2+ signalling in Toxoplasma gondii.
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 91 citations in OpenAlex.
- A divergent cyclic nucleotide binding protein promotes Plasmodium ookinete infection of the mosquito.PLoS pathogens · 2025Article
- 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
- Adaptations and metabolic evolution of myzozoan protists across diverse lifestyles and environments.Microbiology and molecular biology reviews : MMBR · 2024Review
- Dense granule protein 41 of Neospora caninum modulates tachyzoite egress by regulating microneme secretion.Parasitology research · 2024Article
- Orthologs ofMicrobiology spectrum · 2024Article
- Toxoplasma FER1 is a versatile and dynamic mediator of differential microneme trafficking and microneme exocytosis.Scientific reports · 2024Article
- Proteomic approaches for protein kinase substrate identification in Apicomplexa.Molecular and biochemical parasitology · 2024Review
- SPARK regulates AGC kinases central to theeLife · 2024Article
- SPARK regulates AGC kinases central to thebioRxiv : the preprint server for biology · 2024Article
- Purine nucleosides replace cAMP in allosteric regulation of PKA in trypanosomatid pathogens.eLife · 2024Article
- Review
- Article
- Article
- A positive feedback loop mediates crosstalk between calcium, cyclic nucleotide and lipid signalling in calcium-induced Toxoplasma gondii egress.PLoS pathogens · 2022Article
- The beta subunit of AMP-activated protein kinase is critical for cell cycle progression and parasite development in Toxoplasma gondii.Cellular and molecular life sciences : CMLS · 2022Article
- Temporal and thermal profiling of theeLife · 2022Article
- The Tyrosine Phosphatase PRL Regulates Attachment of Toxoplasma gondii to Host Cells and Is Essential for Virulence.mSphere · 2022Article
- Screening the Toxoplasma kinome with high-throughput tagging identifies a regulator of invasion and egress.Nature microbiology · 2022Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 4 countries.
Funding
Abstract
The phylum Apicomplexa comprises a group of obligate intracellular parasites that alternate between intracellular replicating stages and actively motile extracellular forms that move through tissue. Parasite cytosolic Ca2+ signalling activates motility, but how this is switched off after invasion is complete to allow for replication to begin is not understood. Here, we show that the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A catalytic subunit 1 (PKAc1) of Toxoplasma is responsible for suppression of Ca2+ signalling upon host cell invasion. We demonstrate that PKAc1 is sequestered to the parasite periphery by dual acylation of PKA regulatory subunit 1 (PKAr1). Upon genetic depletion of PKAc1 we show that newly invaded parasites exit host cells shortly thereafter, in a perforin-like protein 1 (PLP-1)-dependent fashion. Furthermore, we demonstrate that loss of PKAc1 prevents rapid down-regulation of cytosolic [Ca2+] levels shortly after invasion. We also provide evidence that loss of PKAc1 sensitises parasites to cyclic GMP (cGMP)-induced Ca2+ signalling, thus demonstrating a functional link between cAMP and these other signalling modalities. Together, this work provides a new paradigm in understanding how Toxoplasma and related apicomplexan parasites regulate infectivity.
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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.