An internal sequence targets Trypanosoma brucei triosephosphate isomerase to glycosomes.
In kinetoplastid protists, glycolysis is compartmentalized in glycosomes, organelles belonging to the peroxisome family. The Trypanosoma brucei glycosomal enzyme triosephosphate isomerase (TPI) does not contain either of the two established peroxisome-targeting signals, but we identified a 22 amino acids long fragment, present at an internal position of the polypeptide, that has the capacity to route a reporter protein to glycosomes in transfected trypanosomes, as demonstrated by cell-fractionation experiments and corroborating immunofluorescence studies. This polypeptide-internal routing information seems to be unique for the sequence of the trypanosome enzyme: a reporter protein fused to a Saccharomyces cerevisiae peptide containing the sequence corresponding to the 22-residue fragment of the T. brucei enzyme, was not targeted to glycosomes. In yeasts, as in most other organisms, TPI is indeed exclusively present in the cytosol. These results suggest that it may be possible to develop new trypanocidal drugs by targeting specifically the glycosome import mechanism of TPI.
Research Unit for Tropical Diseases, de Duve Institute and Laboratory of Biochemistry, Université catholique de Louvain, TROP 74.39, Avenue Hippocrate 74, B-1200 Brussels, Belgium.
Nathalie
N
Galland
Stéphane
S
de Walque
Frank G J
FG
Voncken
Christophe L M J
CL
Verlinde
Paul A M
PA
Michels
D000595:Amino Acid Sequence; D000818:Animals; D002458:Cell Fractionation; D017930:Genes, Reporter; D008830:Microbodies / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014305:Triose-Phosphate Isomerase / Q000235:genetics* / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000201:enzymology / Q000502:physiology*
D021382:Protein Sorting Signals; D014305:Triose-Phosphate Isomerase