ArticleThe Journal of biological chemistry2016
Using a Genetically Encoded Sensor to Identify Inhibitors of Toxoplasma gondii Ca2+ Signaling.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 82 citations in OpenAlex.
- Article
- Unveiling the impact of cGMP-dependent protein kinase of Neospora caninum on calcium fluxes and egress functions through quantitative phosphoproteome analysis.Communications biology · 2025Article
- The contribution of the Golgi and the endoplasmic reticulum to calcium and pH homeostasis in Toxoplasma gondii.The Journal of biological chemistry · 2025Article
- Phospho-relay feedback loops control egress vs. intracellular development in Toxoplasma gondii.Cell reports · 2025Article
- The malaria parasite PP1 phosphatase controls the initiation of the egress pathway of asexual blood-stages by regulating the rounding-up of the vacuole.PLoS pathogens · 2025Article
- Orthologs ofMicrobiology spectrum · 2024Article
- Calcium-binding protein TgpCaBP regulates calcium storage of the zoonotic parasiteMicrobiology spectrum · 2024Article
- SPARK regulates AGC kinases central to theeLife · 2024Article
- SPARK regulates AGC kinases central to thebioRxiv : the preprint server for biology · 2024Article
- Review
- A conserved complex of microneme proteins mediates rhoptry discharge in Toxoplasma.The EMBO journal · 2023Article
- 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
- Temporal and thermal profiling of theeLife · 2022Article
- Screening the Toxoplasma kinome with high-throughput tagging identifies a regulator of invasion and egress.Nature microbiology · 2022Article
- Functional Analysis of the Expanded Phosphodiesterase Gene Family in Toxoplasma gondii Tachyzoites.mSphere · 2022Article
- Article
- Calcium signaling in intracellular protist parasites.Current opinion in microbiology · 2021Review
- Chemoproteomics for Plasmodium Parasite Drug Target Discovery.Chembiochem : a European journal of chemical biology · 2021Review
- Article
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
The life cycles of apicomplexan parasites progress in accordance with fluxes in cytosolic Ca(2+) Such fluxes are necessary for events like motility and egress from host cells. We used genetically encoded Ca(2+) indicators (GCaMPs) to develop a cell-based phenotypic screen for compounds that modulate Ca(2+) signaling in the model apicomplexan Toxoplasma gondii In doing so, we took advantage of the phosphodiesterase inhibitor zaprinast, which we show acts in part through cGMP-dependent protein kinase (protein kinase G; PKG) to raise levels of cytosolic Ca(2+) We define the pool of Ca(2+) regulated by PKG to be a neutral store distinct from the endoplasmic reticulum. Screening a library of 823 ATP mimetics, we identify both inhibitors and enhancers of Ca(2+) signaling. Two such compounds constitute novel PKG inhibitors and prevent zaprinast from increasing cytosolic Ca(2+) The enhancers identified are capable of releasing intracellular Ca(2+) stores independently of zaprinast or PKG. One of these enhancers blocks parasite egress and invasion and shows strong antiparasitic activity against T. gondii The same compound inhibits invasion of the most lethal malaria parasite, Plasmodium falciparum Inhibition of Ca(2+)-related phenotypes in these two apicomplexan parasites suggests that depletion of intracellular Ca(2+) stores by the enhancer may be an effective antiparasitic strategy. These results establish a powerful new strategy for identifying compounds that modulate the essential parasite signaling pathways regulated by Ca(2+), underscoring the importance of these pathways and the therapeutic potential of their inhibition.
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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.