Trypanosoma brucei Bloodstream Forms Depend upon Uptake of myo-Inositol for Golgi Complex Phosphatidylinositol Synthesis and Normal Cell Growth

Eukaryot Cell. 2015 Jun;14(6):616-24. doi: 10.1128/EC.00038-15. Epub 2015 Apr 17.


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 complex. We now provide evidence that the Golgi complex-localized T. brucei H(+)-linked myo-inositol transporter (TbHMIT) is essential in bloodstream-form T. brucei. Downregulation 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 tolerates only 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Golgi Apparatus / metabolism*
  • Inositol / metabolism*
  • Phosphatidylinositols / biosynthesis
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Symporters / genetics
  • Symporters / metabolism*
  • Trypanosoma brucei brucei / growth & development
  • Trypanosoma brucei brucei / metabolism*
  • Xenopus


  • Phosphatidylinositols
  • Protozoan Proteins
  • Symporters
  • Inositol