ArticleGenes & development2010
A novel phosphatase cascade regulates differentiation in Trypanosoma brucei via a glycosomal signaling pathway.
Article in Genes & development, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 117 citations in OpenAlex.
- Glycerol metabolism triggers trypanosome differentiation into transmissible forms in mammalian tissue-like conditions.Nature communications · 2026Article
- Phenotypic screening reveals a highly selective phthalimide-based compound with antileishmanial activity.PLoS neglected tropical diseases · 2024Article
- Allostery in Protein Tyrosine Phosphatases is Enabled by Divergent Dynamics.Journal of chemical information and modeling · 2024Article
- Early cellular events and potential regulators of cellulase induction in Penicillium janthinellum NCIM 1366.Scientific reports · 2023Article
- The genomic basis of host and vector specificity in non-pathogenic trypanosomatids.Biology open · 2022Article
- Article
- Delineating transitions during the evolution of specialised peroxisomes: Glycosome formation in kinetoplastid and diplonemid protists.Frontiers in cell and developmental biology · 2022Article
- Article
- Redistribution of FLAgellar Member 8 during the trypanosome life cycle: Consequences for cell fate prediction.Cellular microbiology · 2021Article
- In vitro culture of freshly isolated Trypanosoma brucei brucei bloodstream forms results in gene copy-number changes.PLoS neglected tropical diseases · 2021Article
- Parasite protein phosphatases: biological function, virulence, and host immune evasion.Parasitology research · 2021Review
- Divergent metabolism between Trypanosoma congolense and Trypanosoma brucei results in differential sensitivity to metabolic inhibition.PLoS pathogens · 2021Article
- Right place, right time: Environmental sensing and signal transduction directs cellular differentiation and motility in Trypanosoma brucei.Molecular microbiology · 2021Review
- Identification of positive and negative regulators in the stepwise developmental progression towards infectivity in Trypanosoma brucei.Scientific reports · 2021Article
- An Alba-domain protein required for proteome remodelling during trypanosome differentiation and host transition.PLoS pathogens · 2021Article
- The phosphoinositide regulatory network in Trypanosoma brucei: Implications for cell-wide regulation in eukaryotes.PLoS neglected tropical diseases · 2020Review
- Suramin exposure alters cellular metabolism and mitochondrial energy production in African trypanosomes.The Journal of biological chemistry · 2020Article
- Cell-based and multi-omics profiling reveals dynamic metabolic repurposing of mitochondria to drive developmental progression of Trypanosoma brucei.PLoS biology · 2020Article
- A Global Analysis of Enzyme Compartmentalization to Glycosomes.Pathogens (Basel, Switzerland) · 2020Article
- Phosphoinositide signaling and regulation in Trypanosoma brucei: Specialized functions in a protozoan pathogen.PLoS pathogens · 2020Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
In the mammalian bloodstream, the sleeping sickness parasite Trypanosoma brucei is held poised for transmission by the activity of a tyrosine phosphatase, TbPTP1. This prevents differentiation of the transmissible "stumpy forms" until entry into the tsetse fly, whereupon TbPTP1 is inactivated and major changes in parasite physiology are initiated to allow colonization of the arthropod vector. Using a substrate-trapping approach, we identified the downstream step in this developmental signaling pathway as a DxDxT phosphatase, TbPIP39, which is activated upon tyrosine phosphorylation, and hence is negatively regulated by TbPTP1. In vitro, TbPIP39 promotes the activity of TbPTP1, thereby reinforcing its own repression, this being alleviated by the trypanosome differentiation triggers citrate and cis-aconitate, generating a potentially bistable regulatory switch. Supporting a role in signal transduction, TbPIP39 becomes rapidly tyrosine-phosphorylated during differentiation, and RNAi-mediated transcript ablation in stumpy forms inhibits parasite development. Interestingly, TbPIP39 localizes in glycosomes, peroxisome-like organelles that compartmentalize the trypanosome glycolytic reactions among other enzymatic activities. Our results invoke a phosphatase signaling cascade in which the developmental signal is trafficked to a unique metabolic organelle in the parasite: the glycosome. This is the first characterized environmental signaling pathway targeted directly to a peroxisome-like organelle in any eukaryotic cell.
Indexed as
Identifiers
What OpenQuestion holds
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.