ArticleEukaryotic cell2011
Ubiquitylation and developmental regulation of invariant surface protein expression in trypanosomes.
Article in Eukaryotic cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- Article
- Targeted protein degradation might present a novel therapeutic approach in the fight against African trypanosomiasis.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2023Article
- The role of invariant surface glycoprotein 75 in xenobiotic acquisition by African trypanosomes.Microbial cell (Graz, Austria) · 2023Article
- Biogenesis of extracellular vesicles in protozoan parasites: The ESCRT complex in the trafficking fast lane?PLoS pathogens · 2023Review
- A multifaceted strategy to improve recombinant expression and structural characterisation of a Trypanosoma invariant surface protein.Scientific reports · 2022Article
- The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples.Pathogens (Basel, Switzerland) · 2021Article
- Physiological and proteomic profiles of Trypanosoma brucei rhodesiense parasite isolated from suramin responsive and non-responsive HAT patients in Busoga, Uganda.International journal for parasitology. Drugs and drug resistance · 2021Article
- Late ESCRT machinery mediates the recycling and Rescue of Invariant Surface Glycoprotein 65 in Trypanosoma brucei.Cellular microbiology · 2020Article
- Instability of aquaglyceroporin (AQP) 2 contributes to drug resistance in Trypanosoma brucei.PLoS neglected tropical diseases · 2020Article
- Suramin exposure alters cellular metabolism and mitochondrial energy production in African trypanosomes.The Journal of biological chemistry · 2020Article
- Ubiquitination and the Proteasome as Drug Targets in Trypanosomatid Diseases.Frontiers in chemistry · 2020Review
- SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes.EMBO reports · 2019Article
- Proteome turnover in the bloodstream and procyclic forms ofWellcome open research · 2019Article
- Review
- Rab11 mediates selective recycling and endocytic trafficking in Trypanosoma brucei.Traffic (Copenhagen, Denmark) · 2018Article
- Decoding the network of Trypanosoma brucei proteins that determines sensitivity to apolipoprotein-L1.PLoS pathogens · 2018Article
- The role of the PI(3,5)PMolecular and biochemical parasitology · 2017Article
- Exploiting the Achilles' heel of membrane trafficking in trypanosomes.Current opinion in microbiology · 2016Review
- Loss of the BBSome perturbs endocytic trafficking and disrupts virulence of Trypanosoma brucei.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Modulation of the Surface Proteome through Multiple Ubiquitylation Pathways in African Trypanosomes.PLoS pathogens · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The cell surface of Trypanosoma brucei is dominated by the glycosylphosphatidylinositol-anchored variant surface glycoprotein (VSG), which is essential for immune evasion. VSG biosynthesis, trafficking, and turnover are well documented, but trans-membrane domain (TMD) proteins, including the invariant surface glycoproteins (ISGs), are less well characterized. Internalization and degradation of ISG65 depend on ubiquitylation of conserved cytoplasmic lysines. Using epitope-tagged ISG75 and reporter chimeric proteins bearing the cytoplasmic and trans-membrane regions of ISG75, together with multiple mutants with lysine-to-arginine mutations, we demonstrate that the cytoplasmic tail of ISG75 is both sufficient and necessary for endosomal targeting and degradation. The ISG75 chimeric reporter protein localized to endocytic organelles, while lysine-null versions were significantly stabilized at the cell surface. Importantly, ISG75 cytoplasmic lysines are modified by extensive oligoubiquitin chains and ubiquitylation is abolished in the lysine-null version. Furthermore, we find evidence for differential modes of turnover of ISG65 and ISG75. Full-length lysine-null ISG65 localization and protein turnover are significantly perturbed, but ISG75 localization and protein turnover are not, while ubiquitin conjugates can be detected for full-length lysine-null ISG75 but not ISG65. We find that the ISG75 ectodomain has a predicted coiled-coil, suggesting that ISG75 could be part of a complex, while ISG65 behaves independently. We also demonstrate a developmental stage-specific mechanism for exclusion of surface ISG expression in insect-stage cells by a ubiquitin-independent mechanism. We suggest that ubiquitylation may be a general mechanism for regulating trans-membrane domain surface proteins in trypanosomes.
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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.