TARGETING PROTEINS TO THE GLYCOSOMES OF AFRICAN TRYPANOSOMES

Glycosomes are microbodies found in protozoa belonging to the order Ki netoplastida. These highly specialized organelles compartmentalize mos t of the glycolytic enzymes normally located in the cytosol of other e ukaryotic cells. The recent success in expressing foreign proteins in Trypanosoma brucei has permitted a detailed analysis of glycosomal pro tein targeting signals in these organisms. These studies have revealed that the previously identified C-terminal tripeptide peroxisomal targ eting signal also functions in the import of proteins into the glycoso mes of T. brucei. However, the glycosomal and peroxisomal targeting si gnals differ in a few important ways. The C-terminal tripeptide sequen ce requirements for glycosomal protein targeting are comparatively rel axed. 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 degenera te tripeptide sequence differs significantly from the more stringent r equirements observed for the import of proteins into mammalian peroxis omes and thus represents an opportunity for designing peptide analogue s 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 tar geting signal has tentatively been identified in at least one of the g lycosomal proteins that can target a reporter protein to the glycosome s of T. brucei. Glycosome-deficient mutants have been isolated recentl y, which will aid in the identification of genes involved in the bioge nesis of the glycosome.