GCN2-like eIF2α kinase manages the amino acid starvation response in Toxoplasma gondii.

摘要: The apicomplexan protozoan Toxoplasma gondii is a significant human and veterinary pathogen. As an obligate intracellular parasite, depends on nutrients provided by the host cell needs to adapt limitations in available resources. In mammalian cells, translational regulation via GCN2 phosphorylation of alpha subunit eukaryotic translation initiation factor 2 (eIF2α) key mechanism for adapting nutrient stress. encodes two GCN2-like protein kinases, TgIF2K-C TgIF2K-D. We previously showed that TgIF2K-D phosphorylates T. eIF2α (TgIF2α) upon egress from cell, which enables parasite overcome exposure extracellular environment. However, function remained unresolved. To determine functions we cloned cDNA encoding generated knockout parasites this TgIF2α kinase study its during lytic cycle. did not exhibit fitness defect compared with parental parasites. infection fibroblasts were subsequently cultured glutamine-free medium, impeded induced 50% reduction number plaques formed Furthermore, found growth media was phenocopied expressing only non-phosphorylatable (TgIF2α-S71A), but knockout. These studies suggest kinases evolved have distinct roles changes parasite’s