Targeting Proteins to the Glycosomes of African Trypanosomes

Glycosomes are microbodies found in protozoa belonging to the order Kinetoplastida. These highly specialized organelles compartmentalize most of the glycolytic enzymes normally located in the cytosol of other eukaryotic cells. The recent success in expressing foreign proteins in Trypanosoma brucei has permitted a detailed analysis of glycosomal protein targeting signals in these organisms. These studies have revealed that the previously identified C-terminal tripeptide peroxisomal targeting signal also functions in the import of proteins into the glycosomes of T. brucei. However, the glycosomal and peroxisomal targeting signals differ in a few important ways. The C-terminal tripeptide sequence requirements for glycosomal protein targeting are comparatively relaxed. Of the three C-terminal amino acids, the first can be any small, neutral amino acid; the second should be capable of forming hydrogen bondings, whereas the third is a hydrophobic amino acid. This degenerate tripeptide sequence differs significantly from the more stringent requirements observed for the import of proteins into mammalian peroxisomes and thus represents an opportunity for designing peptide analogues that specifically block the glycosomal protein import for a possible antitrypanosomal chemotherapy. A recently described N-terminal signal that targets thiolase to the mammalian peroxisomes does not appear to function in import into the glycosomes. However, a novel internal targeting signal has tentatively been identified in at least one of the glycosomal proteins that can target a reporter protein to the glycosomes of T. brucei. Glycosome-deficient mutants have been isolated recently, which will aid in the identification of genes involved in the biogenesis of the glycosome.