ArticleProceedings of the National Academy of Sciences of the United States of America2014
Toxoplasma GRA7 effector increases turnover of immunity-related GTPases and contributes to acute virulence in the mouse.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 135 citations in OpenAlex.
- Short linear motifs-underexplored players drivingMicrobiology spectrum · 2026Article
- Toxoplasma GRA72 is Involved in Membrane-Associated Functions and Metabolic Homeostasis Revealed by Transcriptomic Analysis.Acta parasitologica · 2026Article
- Dense granule proteins: key mediators ofFrontiers in medicine · 2026Review
- Intra-strain genetic heterogeneity in Toxoplasma gondii ME49: Oxford Nanopore long-read sequencing reveals copy number variation in the ROP8-ROP2A locus.BMC genomics · 2025Article
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- Influenza virus-like particles presentingNanomedicine (London, England) · 2025Article
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- Molecular interactions ofFrontiers in veterinary science · 2025Article
- TBC9, an essential TBC-domain protein, regulates early vesicular transport and IMC formation in Toxoplasma gondii.Communications biology · 2024Article
- Trx4, a novel thioredoxin protein, is important for Toxoplasma gondii fitness.Parasites & vectors · 2024Article
- Host E3 ubiquitin ligase ITCH mediatesmBio · 2024Article
- Susceptibility ofmBio · 2024Article
- Toxoplasma protein export and effector function.Nature microbiology · 2024Review
- IFNs in host defence and parasite immune evasion duringFrontiers in immunology · 2024Review
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- Structural basis of Irgb6 inactivation by Toxoplasma gondii through the phosphorylation of switch I.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- Host E3 ubiquitin ligase ITCH mediatesbioRxiv : the preprint server for biology · 2023Article
- Functional screening revealsmBio · 2023Article
- The Toxoplasma micropore mediates endocytosis for selective nutrient salvage from host cell compartments.Nature communications · 2023Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The intracellular parasite Toxoplasma gondii enjoys a wide host range and is adept at surviving in both naive and activated macrophages. Previous studies have emphasized the importance of the active serine-threonine protein kinase rhoptry protein 18 (ROP18), which targets immunity-related GTPases (IRGs), in mediating macrophage survival and acute virulence of T. gondii in mice. Here, we demonstrate that ROP18 exists in a complex with the pseudokinases rhoptry proteins 8 and 2 (ROP8/2) and dense granule protein 7 (GRA7). Individual deletion mutant gra7 or rop18 was partially attenuated for virulence in mice, whereas the combined gra7rop18 mutant was avirulent, suggesting these proteins act together in the same pathway. The virulence defect of the double mutant was mirrored by increased recruitment of IRGs and clearance of the parasite in IFN-γ-activated macrophages in vitro. GRA7 was shown to recognize a conserved feature of IRGs, binding directly to the active dimer of immunity-related GTPase a6 in a GTP-dependent manner. Binding of GRA7 to immunity-related GTPase a6 led to enhanced polymerization, rapid turnover, and eventual disassembly. Collectively, these studies suggest that ROP18 and GRA7 act in a complex to target IRGs by distinct mechanisms that are synergistic.
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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.