myo-Inositol uptake is essential for bulk inositol phospholipid but not glycosylphosphatidylinositol synthesis in Trypanosoma brucei

Gonzalez-Salgado, Amaia; Steinmann, Michael E; Greganova, Eva; Rauch, Monika; Mäser, Pascal; Sigel, Erwin; Bütikofer, Peter (2012). myo-Inositol uptake is essential for bulk inositol phospholipid but not glycosylphosphatidylinositol synthesis in Trypanosoma brucei. Journal of biological chemistry, 287(16), pp. 13313-23. Bethesda, Md.: American Society for Biochemistry and Molecular Biology 10.1074/jbc.M112.344812

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Steinmann, Michael Eduard, Rauch, Monika, Sigel, Erwin, Bütikofer, Peter

ISSN:

0021-9258

Publisher:

American Society for Biochemistry and Molecular Biology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:37

Last Modified:

05 Dec 2022 14:11

Publisher DOI:

10.1074/jbc.M112.344812

PubMed ID:

22351763

Web of Science ID:

000302903700067

URI:

https://boris.unibe.ch/id/eprint/15038 (FactScience: 222192)

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