ArticleMolecular biology of the cell2018
Endoplasmic reticulum-associated degradation and disposal of misfolded GPI-anchored proteins in Trypanosoma brucei.
Article in Molecular biology of the cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Mechanisms of Quality Control in GPI-Anchored Proteins: The Central Role of the Lipid Anchor.International journal of molecular sciences · 2026Review
- To Explore Potential Natural Inhibitors of Cysteine Proteases to Combat Human African Trypanosomiasis and Chagas Disease.Current medicinal chemistry · 2026Review
- New frontiers in quality control: the case of GPI-anchored proteins.Nature reviews. Molecular cell biology · 2023Article
- The endoplasmic reticulum of trypanosomatids: An unrevealed road for chemotherapy.Frontiers in cellular and infection microbiology · 2022Review
- Article
- p67: a cryptic lysosomal hydrolase inParasitology · 2021Article
- Article
- Dropping anchor: stringent quality control prevents GPI anchoring of severely misfolded proteins in plants.Plant physiology · 2021Article
- The Glycosylphosphatidylinositol Anchor: A Linchpin for Cell Surface Versatility of Trypanosomatids.Frontiers in cell and developmental biology · 2021Review
- Trypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyase.PLoS neglected tropical diseases · 2020Article
- Instability of aquaglyceroporin (AQP) 2 contributes to drug resistance in Trypanosoma brucei.PLoS neglected tropical diseases · 2020Article
- Ubiquitination and the Proteasome as Drug Targets in Trypanosomatid Diseases.Frontiers in chemistry · 2020Review
- Evolution of Antigenic Variation in African Trypanosomes: Variant Surface Glycoprotein Expression, Structure, and Function.BioEssays : news and reviews in molecular, cellular and developmental biology · 2018Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Misfolded secretory proteins are retained by endoplasmic reticulum quality control (ERQC) and degraded in the proteasome by ER-associated degradation (ERAD). However, in yeast and mammals, misfolded glycosylphosphatidylinositol (GPI)-anchored proteins are preferentially degraded in the vacuole/lysosome. We investigate this process in the divergent eukaryotic pathogen Trypanosoma brucei using a misfolded GPI-anchored subunit (HA:E6) of the trypanosome transferrin receptor. HA:E6 is N-glycosylated and GPI-anchored and accumulates in the ER as aggregates. Treatment with MG132, a proteasome inhibitor, generates a smaller protected polypeptide (HA:E6*), consistent with turnover in the proteasome. HA:E6* partitions between membrane and cytosol fractions, and both pools are proteinase K-sensitive, indicating cytosolic disposition of membrane-associated HA:E6*. HA:E6* is de-N-glycosylated and has a full GPI-glycan structure from which dimyristoylglycerol has been removed, indicating that complete GPI removal is not a prerequisite for proteasomal degradation. However, HA:E6* is apparently not ubiquitin-modified. The trypanosome GPI anchor is a forward trafficking signal; thus the dynamic tension between ERQC and ER exit favors degradation by ERAD. These results differ markedly from the standard eukaryotic model systems and may indicate an evolutionary advantage related to pathogenesis.
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