title: myo-Inositol uptake is essential for bulk inositol phospholipid but not glycosylphosphatidylinositol synthesis in Trypanosoma brucei.
abstract: myo-Inositol is an essential precursor for the production of inositol phosphates and inositol phospholipids in all eukaryotes. Intracellular myo-inositol is generated by de novo synthesis from glucose 6-phosphate or is provided from the environment via myo-inositol symporters. We show that in Trypanosoma brucei, the causative pathogen of human African sleeping sickness and nagana in domestic animals, myo-inositol is taken up via a specific proton-coupled electrogenic symport and that this transport is essential for parasite survival in culture. Down-regulation of the myo-inositol transporter using RNA interference inhibited uptake of myo-inositol and blocked the synthesis of the myo-inositol-containing phospholipids, phosphatidylinositol and inositol phosphorylceramide; in contrast, it had no effect on glycosylphosphatidylinositol production. This together with the unexpected localization of the myo-inositol transporter in both the plasma membrane and the Golgi demonstrate that metabolism of endogenous and exogenous myo-inositol in T. brucei is strictly segregated.
authors.affiliation: Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland.
authors.forename: Amaia
authors.initials: A
authors.lastname: Gonzalez-Salgado
authors.forename: Michael E
authors.initials: ME
authors.lastname: Steinmann
authors.forename: Eva
authors.initials: E
authors.lastname: Greganova
authors.forename: Monika
authors.initials: M
authors.lastname: Rauch
authors.forename: Pascal
authors.initials: P
authors.lastname: Mäser
authors.forename: Erwin
authors.initials: E
authors.lastname: Sigel
authors.forename: Peter
authors.initials: P
authors.lastname: Bütikofer
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D017125:Genes, Protozoan / Q000502:physiology; D017261:Glycosylphosphatidylinositols / Q000096:biosynthesis*; D007294:Inositol / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology; D010641:Phenotype; D010716:Phosphatidylinositols / Q000096:biosynthesis*; D010802:Phylogeny; D034622:RNA Interference; D016053:RNA, Protozoan / Q000378:metabolism; D014316:Tritium; D014346:Trypanosoma brucei brucei / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D014981:Xenopus
chemical_list: D002352:Carrier Proteins; D017261:Glycosylphosphatidylinositols; D010716:Phosphatidylinositols; D016053:RNA, Protozoan; D014316:Tritium; D007294:Inositol