London School of Hygiene & Tropical Medicine. 2017. Identification of Trypanosoma brucei apolipoprotein-L1 sensitivity determinants by RNAi library selection. [Online]. European Nucleotide Archive. Available from: https://www.ebi.ac.uk/ena/data/view/PRJEB23779
London School of Hygiene & Tropical Medicine. Identification of Trypanosoma brucei apolipoprotein-L1 sensitivity determinants by RNAi library selection [Internet]. European Nucleotide Archive; 2017. Available from: https://www.ebi.ac.uk/ena/data/view/PRJEB23779
London School of Hygiene & Tropical Medicine (2017). Identification of Trypanosoma brucei apolipoprotein-L1 sensitivity determinants by RNAi library selection. [Data Collection]. European Nucleotide Archive. https://www.ebi.ac.uk/ena/data/view/PRJEB23779
Alternative Title
Project: PRJEB23779
Description
In contrast to Trypanosoma brucei gambiense and T. b. rhodesiense (the causative agents of human African trypanosomiasis), T. b. brucei is lysed by apolipoprotein-L1 (apoL1)-containing human serum trypanolytic factors (TLF), rendering it non-infectious to humans. Selecting our bloodstream-form T. b. brucei RNAi library with recombinant apoL1 identified an array of factors that supports the trypanocidal action of apoL1, including six putative ubiquitin modifiers and several proteins putatively involved in membrane trafficking; we also identified the known apoL1 sensitivity determinants, TbKIFC1 and the V-ATPase. Most prominent amongst the novel apoL1 sensitivity determinants was a putative ubiquitin ligase. Intriguingly, while loss of this ubiquitin ligase reduces parasite sensitivity to apoL1, its loss enhances parasite sensitivity to TLF1-dominated normal human serum, indicating that free and TLF1-bound apoL1 have contrasting modes-of-action. Indeed, loss of the known human serum sensitivity determinants, p67 (lysosomal associated membrane protein) and the cathepsin-L regulator, ‘inhibitor of cysteine peptidase’, had no effect on sensitivity to free apoL1. Our findings highlight a complex network of proteins that influences apoL1 action, with implications for our understanding of the anti-trypanosomal action of human serum.
Additional information
Secondary Study Accession:ERP105557
Keywords
Data capture method | Experiment |
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Date (Date published in a 3rd party system) | 5 December 2017 |
Language(s) of written materials | English |
Data Creators | London School of Hygiene & Tropical Medicine |
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LSHTM Faculty/Department | Faculty of Infectious and Tropical Diseases |
Participating Institutions | London School of Hygiene & Tropical Medicine, London, United Kingdom |
Date Deposited | 01 May 2020 10:59 |
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Last Modified | 01 May 2020 10:59 |
Publisher | European Nucleotide Archive |