ArticleThe Journal of biological chemistry2012
Conditional mutagenesis of a novel choline kinase demonstrates plasticity of phosphatidylcholine biogenesis and gene expression in Toxoplasma gondii.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- An ER-IMC bridge protein TgVPS13A and an IMC-resident scramblase TgDAT1 drive daughter budding in Toxoplasma gondii.PLoS pathogens · 2026Article
- Sarcoendoplasmic reticulum calcium ATPase is an essential and druggable lipid-dependent ion pump in Toxoplasma gondii.Communications biology · 2025Article
- Lipid metabolism: the potential targets for toxoplasmosis treatment.Parasites & vectors · 2024Review
- Synthesis vs. salvage of ester- and ether-linked phosphatidylethanolamine in the intracellular protozoan pathogen Toxoplasma gondii.Communications biology · 2023Article
- Apically-located P4-ATPase1-Lem1 complex internalizes phosphatidylserine and regulates motility-dependent invasion and egress inComputational and structural biotechnology journal · 2023Article
- Metabolic flexibilities and vulnerabilities in the pentose phosphate pathway of the zoonotic pathogen Toxoplasma gondii.PLoS pathogens · 2022Article
- Screening the Toxoplasma kinome with high-throughput tagging identifies a regulator of invasion and egress.Nature microbiology · 2022Article
- Phosphatidylinositol synthesis, its selective salvage, and inter-regulation of anionic phospholipids in Toxoplasma gondii.Communications biology · 2020Article
- ChoK-ing the Pathogenic Bacteria: Potential of Human Choline Kinase Inhibitors as Antimicrobial Agents.BioMed research international · 2020Review
- A CTP Synthase Undergoing Stage-Specific Spatial Expression Is Essential for the Survival of the Intracellular ParasiteFrontiers in cellular and infection microbiology · 2018Article
- Two phylogenetically and compartmentally distinct CDP-diacylglycerol synthases cooperate for lipid biogenesis inThe Journal of biological chemistry · 2017Article
- Novel insights into the composition and function of the Toxoplasma IMC sutures.Cellular microbiology · 2017Article
- Phosphatidylethanolamine synthesis in the parasite mitochondrion is required for efficient growth but dispensable for survival of Toxoplasma gondii.The Journal of biological chemistry · 2014Article
- Lipid synthesis in protozoan parasites: a comparison between kinetoplastids and apicomplexans.Progress in lipid research · 2013Review
- Microbial modulation of host immunity with the small molecule phosphorylcholine.Infection and immunity · 2013Review
- Article
- Aminoglycerophospholipid flipping and P4-ATPases in Toxoplasma gondii.The Journal of biological chemistryArticle
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Authors and funding
9 authors.
Funding
Abstract
The obligate intracellular and promiscuous protozoan parasite Toxoplasma gondii needs an extensive membrane biogenesis that must be satisfied irrespective of its host-cell milieu. We show that the synthesis of the major lipid in T. gondii, phosphatidylcholine (PtdCho), is initiated by a novel choline kinase (TgCK). Full-length (∼70-kDa) TgCK displayed a low affinity for choline (K(m) ∼0.77 mM) and harbors a unique N-terminal hydrophobic peptide that is required for the formation of enzyme oligomers in the parasite cytosol but not for activity. Conditional mutagenesis of the TgCK gene in T. gondii attenuated the protein level by ∼60%, which was abolished in the off state of the mutant (Δtgck(i)). Unexpectedly, the mutant was not impaired in its growth and exhibited a normal PtdCho biogenesis. The parasite compensated for the loss of full-length TgCK by two potential 53- and 44-kDa isoforms expressed through a cryptic promoter identified within exon 1. TgCK-Exon1 alone was sufficient in driving the expression of GFP in E. coli. The presence of a cryptic promoter correlated with the persistent enzyme activity, PtdCho synthesis, and susceptibility of T. gondii to a choline analog, dimethylethanolamine. Quite notably, the mutant displayed a regular growth in the off state despite a 35% decline in PtdCho content and lipid synthesis, suggesting a compositional flexibility in the membranes of the parasite. The observed plasticity of gene expression and membrane biogenesis can ensure a faithful replication and adaptation of T. gondii in disparate host or nutrient environments.
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