| Autor: |
Lecordier, Laurence, Uzureau, Pierrick, Tebabi, Patricia, Pérez‐Morga, David, Nolan, Derek, Schumann Burkard, Gabriela, Roditi, Isabel, Pays, Etienne |
| Předmět: |
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| Zdroj: |
Molecular Microbiology; Nov2014, Vol. 94 Issue 3, p625-636, 12p, 2 Diagrams, 2 Charts, 6 Graphs |
| Abstrakt: |
Normal human serum ( NHS) confers human resistance to infection by the parasite T rypanosoma 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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