Identification of Trypanosoma brucei components involved in trypanolysis by normal human serum

Lecordier, Laurence; Uzureau, P; Tebabi, P; Perez-Morga, D; Nolan, D; Schumann-Burkard, Gabriela; Roditi, Isabel; Pays, E (2014). Identification of Trypanosoma brucei components involved in trypanolysis by normal human serum. Molecular microbiology, 94(3), pp. 625-636. Blackwell Science 10.1111/mmi.12783

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Normal human serum (NHS) confers human resistance to infection by the parasite Trypanosoma brucei owing to the trypanolytic activity of apolipoprotein L1 (APOL1), present in two serum complexes termed Trypanolytic Factors (TLF-1 and -2). In order to identify parasite components involved in the intracellular trafficking and activity of TLFs, an inducible RNA interference (RNAi) genomic DNA library constructed in bloodstream form T. brucei was subjected to RNAi induction and selection for resistant parasites under NHS conditions favouring either TLF-1 or TLF-2 uptake. While TLF-1 conditions readily selected the haptoglobin-haemoglobin (HP-HB) surface receptor TbHpHbR as expected, given its known ability to bind TLF-1, under TLF-2 conditions no specific receptor for TLF-2 was identified. Instead, the screen allowed the identification of five distinct factors expected to be involved in the assembly of the vacuolar proton pump V-ATPase and consecutive endosomal acidification. These data confirm that lowering the pH during endocytosis is required for APOL1 toxic activity.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Schumann-Burkard, Gabriela and Roditi, Isabel

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

0950-382X

Publisher:

Blackwell Science

Funders:

[UNSPECIFIED] Velux Foundation
[UNSPECIFIED] Howard Hughes Medical Institute

Language:

English

Submitter:

Isabel Roditi

Date Deposited:

08 May 2015 11:19

Last Modified:

09 Sep 2015 10:45

Publisher DOI:

10.1111/mmi.12783

PubMed ID:

25256834

BORIS DOI:

10.7892/boris.68785

URI:

https://boris.unibe.ch/id/eprint/68785

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