ArticlePloS one2011
Protein synthesis attenuation by phosphorylation of eIF2α is required for the differentiation of Trypanosoma cruzi into infective forms.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 58 citations in OpenAlex.
- Remodeling of tRNA modification in Trypanosoma cruzi life forms.PLoS pathogens · 2026Article
- Trypanosoma cruzi eIF4E3- and eIF4E4-containing complexes bind different mRNAs and may sequester inactive mRNAs during nutritional stress.Nucleic acids research · 2025Article
- Branched-chain amino acids modulate the proteomic profile of Trypanosoma cruzi metacyclogenesis induced by proline.PLoS neglected tropical diseases · 2024Article
- Translation initiation factor eIF1.2 promotes Toxoplasma stage conversion by regulating levels of key differentiation factors.Nature communications · 2024Article
- Metacyclogenesis as the Starting Point of Chagas Disease.International journal of molecular sciences · 2023Review
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- Open chromatin analysis in Trypanosoma cruzi life forms highlights critical differences in genomic compartments and developmental regulation at tDNA loci.Epigenetics & chromatin · 2022Article
- The endoplasmic reticulum of trypanosomatids: An unrevealed road for chemotherapy.Frontiers in cellular and infection microbiology · 2022Review
- 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
- RNA Binding Proteins and Gene Expression Regulation inFrontiers in cellular and infection microbiology · 2020Article
- Bioactive lipids regulate Trypanosoma cruzi development.Parasitology research · 2019Article
- Quantitative phosphoproteome and proteome analyses emphasize the influence of phosphorylation events during the nutritional stress of Trypanosoma cruzi: the initial moments of in vitro metacyclogenesis.Cell stress & chaperones · 2019Article
- The RNA-binding protein TcUBP1 up-regulates an RNA regulon for a cell surface-associatedThe Journal of biological chemistry · 2019Article
- Redox Balance Keepers and Possible Cell Functions Managed by Redox Homeostasis inFrontiers in cellular and infection microbiology · 2019Review
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- Article
- Translational repression by an RNA-binding protein promotes differentiation to infective forms in Trypanosoma cruzi.PLoS pathogens · 2018Article
- The Trypanosoma cruzi RNA-binding protein RBP42 is expressed in the cytoplasm throughout the life cycle of the parasite.Parasitology research · 2018Article
- Identification of di-substituted ureas that prevent growth of trypanosomes through inhibition of translation initiation.Scientific reports · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chagas' disease is a potentially life-threatening illness caused by the unicellular protozoan parasite Trypanosoma cruzi. It is transmitted to humans by triatomine bugs where T. cruzi multiplies and differentiates in the digestive tract. The differentiation of proliferative and non-infective epimastigotes into infective metacyclic trypomastigotes (metacyclogenesis) can be correlated to nutrient exhaustion in the gut of the insect vector. In vitro, metacyclic-trypomastigotes can be obtained when epimastigotes are submitted to nutritional stress suggesting that metacyclogenesis is triggered by nutrient starvation. The molecular mechanism underlying such event is not understood. Here, we investigated the role of one of the key signaling responses elicited by nutritional stress in all other eukaryotes, the inhibition of translation initiation by the phosphorylation of the eukaryotic initiation factor 2α (eIF2α), during the in vitro differentiation of T. cruzi. Monospecific antibodies that recognize the phosphorylated Tc-eIF2α form were generated and used to demonstrate that parasites subjected to nutritional stress show increased levels of Tc-eIF2α phosphorylation. This was accompanied by a drastic inhibition of global translation initiation, as determined by polysomal profiles. A strain of T. cruzi overexpressing a mutant Tc-eIF2α, incapable of being phosphorylated, showed a block on translation initiation, indicating that such a nutritional stress in trypanosomatids induces the conserved translation inhibition response. In addition, Tc-eIF2α phosphorylation is critical for parasite differentiation since the overexpression of the mutant eIF2α in epimastigotes abolished metacyclogenesis. This work defines the role of eIF2α phosphorylation as a key step in T. cruzi differentiation.
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