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Characterization of Trypanosoma brucei PEX14 and its role in the import of glycosomal matrix proteins.

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Moyersoen, Juliette [UCL] Choe, Jungwoo Kumar, Abhinav Voncken, Frank G J Hol, Wim G J Michels, Paul [UCL]

It has been shown previously in various organisms that the peroxin PEX14 is a component of a docking complex at the peroxisomal membrane, where it is involved in the import of matrix proteins into the organelle after their synthesis in the cytosol and recognition by a receptor. Here we present a characterization of the Trypanosoma brucei homologue of PEX14. It is shown that the protein is associated with glycosomes, the peroxisome-like organelles of trypanosomatids in which most glycolytic enzymes are compartmentalized. The N-terminal part of the protein binds specifically to TbPEX5, the cytosolic receptor for glycosomal matrix proteins with a peroxisome-targeting signal type 1 (PTS-1). TbPEX14 mRNA depletion by RNA interference results, in both bloodstream-form and procyclic, insect-stage T. brucei, in mislocalization of glycosomal proteins to the cytosol. The mislocalization was observed for different classes of matrix proteins: proteins with a C-terminal PTS-1, a N-terminal PTS-2 and a polypeptide internal I-PTS. The RNA interference experiments also showed that TbPEX14 is essential for the survival of bloodstream-form and procyclic trypanosomes. These data indicate the protein's great potential as a target for selective trypanocidal drugs.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2003
Journal information "European journal of biochemistry / FEBS" - Vol. 270, no. 9, p. 2059-67 (2003)
Peer reviewed yes
issn 0014-2956
Publication status Publié
Affiliation UCL
MESH Subject Animals ; Cell Fractionation ; Digitonin - metabolism ; Immunohistochemistry ; Indicators and Reagents - metabolism ; Membrane Proteins - genetics - metabolism ; Microbodies - chemistry - metabolism ; Molecular Sequence Data ; Protein Transport - physiology ; Protozoan Proteins - genetics - metabolism ; RNA Interference ; Receptors, Cytoplasmic and Nuclear - genetics - metabolism ; Recombinant Proteins - genetics - metabolism ; Trypanosoma brucei brucei - cytology - physiology
Keywords Trypanosome ; Glycosome biogenesis ; PEX14 ; Protein-protein interctions ; RNA interference
Links
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Bibliographic reference Moyersoen, Juliette ; Choe, Jungwoo ; Kumar, Abhinav ; Voncken, Frank G J ; Hol, Wim G J ; et. al. Characterization of Trypanosoma brucei PEX14 and its role in the import of glycosomal matrix proteins.. In: European journal of biochemistry / FEBS, Vol. 270, no. 9, p. 2059-67 (2003)
Permanent URL http://hdl.handle.net/2078.1/9438