ArticleProceedings of the National Academy of Sciences of the United States of America2012
Third target of rapamycin complex negatively regulates development of quiescence in Trypanosoma brucei.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 80 citations in OpenAlex.
- Article
- Insights into the Procedures and Interpretation of Autophagy in Trypanosoma cruzi.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Article
- TORC1 is an essential regulator of nutrient-controlled proliferation and differentiation in Leishmania.EMBO reports · 2024Article
- Pathogenicity and virulence of African trypanosomes: From laboratory models to clinically relevant hosts.Virulence · 2023Review
- FLAgellum Member 8 modulates extravascular distribution of African trypanosomes.PLoS pathogens · 2023Article
- Autophagy in protists and their hosts: When, how and why?Autophagy reports · 2023Article
- Stress- and metabolic responses of Candida albicans require Tor1 kinase N-terminal HEAT repeats.PLoS pathogens · 2022Article
- Redistribution of FLAgellar Member 8 during the trypanosome life cycle: Consequences for cell fate prediction.Cellular microbiology · 2021Article
- The host mTOR pathway and parasitic diseases pathogenesis.Parasitology research · 2021Review
- The Occurrence of Malignancy inFrontiers in microbiology · 2021Article
- Large-Scale Phylogenetic Analysis of Trypanosomatid Adenylate Cyclases Reveals Associations with Extracellular Lifestyle and Host-Pathogen Interplay.Genome biology and evolution · 2020Article
- The phosphoinositide regulatory network in Trypanosoma brucei: Implications for cell-wide regulation in eukaryotes.PLoS neglected tropical diseases · 2020Review
- Exposure of Anopheles mosquitoes to trypanosomes reduces reproductive fitness and enhances susceptibility to Plasmodium.PLoS neglected tropical diseases · 2020Article
- Phosphoinositide signaling and regulation in Trypanosoma brucei: Specialized functions in a protozoan pathogen.PLoS pathogens · 2020Review
- SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes.EMBO reports · 2019Article
- Article
- Non-linear hierarchy of the quorum sensing signalling pathway in bloodstream form African trypanosomes.PLoS pathogens · 2018Article
- Inositol polyphosphate multikinase regulation of Trypanosoma brucei life stage development.Molecular biology of the cell · 2018Article
- RNA-Seq analysis validates the use of culture-derived Trypanosoma brucei and provides new markers for mammalian and insect life-cycle stages.BMC genomics · 2018Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
African trypanosomes are protozoan parasites transmitted by a tsetse fly vector to a mammalian host. The life cycle includes highly proliferative forms and quiescent forms, the latter being adapted to host transmission. The signaling pathways controlling the developmental switch between the two forms remain unknown. Trypanosoma brucei contains two target of rapamycin (TOR) kinases, TbTOR1 and TbTOR2, and two TOR complexes, TbTORC1 and TbTORC2. Surprisingly, two additional TOR kinases are encoded in the T. brucei genome. We report that TbTOR4 associates with an Armadillo domain-containing protein (TbArmtor), a major vault protein, and LST8 to form a unique TOR complex, TbTORC4. Depletion of TbTOR4 caused irreversible differentiation of the parasite into the quiescent form. AMP and hydrolysable analogs of cAMP inhibited TbTOR4 expression and induced the stumpy quiescent form. Our results reveal unexpected complexity in TOR signaling and show that TbTORC4 negatively regulates differentiation of the proliferative form into the quiescent form.
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