Imperial College London
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Dr Calvin Tiengwe

Faculty of Natural Sciences, Department of Life Sciences

Research Fellow (Sir Henry Dale Fellowship)
 
 
 
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Contact

 

+44 (0)20 7594 5260c.tiengwe

 
 
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Location

 

503Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Tiengwe:2018:10.1091/mbc.E18-06-0380,
author = {Tiengwe, CW and Koeller, C and Bangs, J},
doi = {10.1091/mbc.E18-06-0380},
journal = {Molecular Biology of the Cell},
pages = {2359--2507},
title = {ER-associated degradation and disposal of misfolded GPI-anchored proteins in Trypanosoma brucei},
url = {http://dx.doi.org/10.1091/mbc.E18-06-0380},
volume = {29},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Tiengwe,CW
AU  - Koeller,C
AU  - Bangs,J
DO  - 10.1091/mbc.E18-06-0380
EP  - 2507
PY  - 2018///
SN  - 1059-1524
SP  - 2359
TI  - ER-associated degradation and disposal of misfolded GPI-anchored proteins in Trypanosoma brucei
T2  - Molecular Biology of the Cell
UR  - http://dx.doi.org/10.1091/mbc.E18-06-0380
UR  - http://hdl.handle.net/10044/1/62913
VL  - 29
ER  -
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