ArticleInternational journal for parasitology2014
GCN2-like eIF2α kinase manages the amino acid starvation response in Toxoplasma gondii.
Article in International journal for parasitology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- Article
- Translational control of Toxoplasma gondii differentiation.Bioscience reports · 2026Review
- The integrated stress response in apicomplexan and trypanosomatid parasites: balancing survival and pathogenesis.Frontiers in immunology · 2026Review
- Article
- Identification ofmSphere · 2023Article
- CRISPR Screens IdentifymBio · 2023Article
- Multiple Roles of the Stress Sensor GCN2 in Immune Cells.International journal of molecular sciences · 2023Review
- Functional Amino Acids and Autophagy: Diverse Signal Transduction and Application.International journal of molecular sciences · 2021Review
- Substrate-mediated regulation of the arginine transporter of Toxoplasma gondii.PLoS pathogens · 2021Article
- Host sensing and signal transduction during Toxoplasma stage conversion.Molecular microbiology · 2021Review
- Article
- Endoplasmic Reticulum Stress, a Target for Drug Design and Drug Resistance in Parasitosis.Frontiers in microbiology · 2021Review
- GCN2-Like Kinase Modulates Stress Granule Formation During Nutritional Stress inFrontiers in cellular and infection microbiology · 2020Article
- Regulation of arginine transport by GCN2 eIF2 kinase is important for replication of the intracellular parasite Toxoplasma gondii.PLoS pathogens · 2019Article
- Effects of PERK eIF2α Kinase Inhibitor against Toxoplasma gondii.Antimicrobial agents and chemotherapy · 2018Article
- Translation and Translational Control in Dinoflagellates.Microorganisms · 2018Review
- General amino acid control in fission yeast is regulated by a nonconserved transcription factor, with functions analogous to Gcn4/Atf4.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Translational Control in the Latency of Apicomplexan Parasites.Trends in parasitology · 2017Review
- Autophagy participates in the unfolded protein response in Toxoplasma gondii.FEMS microbiology letters · 2017Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The apicomplexan protozoan Toxoplasma gondii is a significant human and veterinary pathogen. As an obligate intracellular parasite, Toxoplasma depends on nutrients provided by the host cell and needs to adapt to limitations in available resources. In mammalian cells, translational regulation via GCN2 phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α) is a key mechanism for adapting to nutrient stress. Toxoplasma encodes two GCN2-like protein kinases, TgIF2K-C and TgIF2K-D. We previously showed that TgIF2K-D phosphorylates T. gondii eIF2α (TgIF2α) upon egress from the host cell, which enables the parasite to overcome exposure to the extracellular environment. However, the function of TgIF2K-C remained unresolved. To determine the functions of TgIF2K-C in the parasite, we cloned the cDNA encoding TgIF2K-C and generated knockout parasites of this TgIF2α kinase to study its function during the lytic cycle. The TgIF2K-C knockout did not exhibit a fitness defect compared with parental parasites. However, upon infection of human fibroblasts that were subsequently cultured in glutamine-free medium, the intracellular TgIF2K-C knockout parasites were impeded for induced phosphorylation of TgIF2α and showed a 50% reduction in the number of plaques formed compared with parental parasites. Furthermore, we found that this growth defect in glutamine-free media was phenocopied in parasites expressing only a non-phosphorylatable TgIF2α (TgIF2α-S71A), but not in a TgIF2K-D knockout. These studies suggest that Toxoplasma GCN2-like kinases TgIF2K-C and TgIF2K-D evolved to have distinct roles in adapting to changes in the parasite's environment.
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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.