Trypanosoma brucei bloodstream forms depend upon uptake of myo-inositol for Golgi phosphatidylinositol synthesis and normal cell growth
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myo-Inositol is a building block for all inositol-containing phospholipids in eukaryotes. It can be synthesized de novo from glucose-6-phosphate in the cytosol and endoplasmic reticulum. Alternatively, it can be taken up from the environment via Na+- or H+-linked myo-inositol transporters. While Na+-coupled myo-inositol transporters are found exclusively in the plasma membrane, H+-linked myo-inositol transporters are detected in intracellular organelles. In Trypanosoma brucei, the causative agent of human African sleeping sickness, myo-inositol metabolism is compartmentalized. De novo synthesized myo-inositol is used for glycosylphosphatidylinositol production in the endoplasmic reticulum, whereas the myo-inositol taken up from the environment is used for bulk phosphatidylinositol synthesis in the Golgi. We now provide evidence that the Golgi localized T. brucei H+-linked myo-inositol transporter (TbHMIT) is essential in bloodstream forms. Down-regulation of TbHMIT expression by RNA interference blocked phosphatidylinositol production and inhibited growth of parasites in culture. Characterization of the transporter in a heterologous expression system demonstrated a remarkable selectivity of TbHMIT for myo-inositol. It only tolerates a single modification on the inositol ring, such as the removal of a hydroxyl group, or the inversion of stereochemistry at a single hydroxyl group relative to myo-inositol.
González-Salgado , A , Steinmann , M , Major , L L , Sigel , E , Reymond , J-L , Smith , T K & Bütikofer , P 2015 , ' Trypanosoma brucei bloodstream forms depend upon uptake of myo -inositol for Golgi phosphatidylinositol synthesis and normal cell growth ' Eukaryotic Cell , vol 14 , no. 6 , pp. 616-624 . DOI: 10.1128/EC.00038-15
© 2015, American Society for Microbiology. This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at ec.asm.org / https://dx.doi.org/10.1128/EC.00038-15
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