Myo-Inositol Uptake is Essential for Bulk Inositol Phospholipid but Not Glycosylphosphatidylinositol Synthesis in Trypanosoma Brucei

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2012 Feb 22

PMID 22351763

Citations 22

Authors

Amaia Gonzalez-Salgado

Michael E Steinmann

Eva Greganova

Monika Rauch

Pascal Maser

Erwin Sigel

Peter Butikofer

Affiliations

Soon will be listed here.

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.

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