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Eukaryot Cell
2015 Jun 01;146:616-24. doi: 10.1128/EC.00038-15.
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Trypanosoma brucei Bloodstream Forms Depend upon Uptake of myo-Inositol for Golgi Complex Phosphatidylinositol Synthesis and Normal Cell Growth.
González-Salgado A
,
Steinmann M
,
Major LL
,
Sigel E
,
Reymond JL
,
Smith TK
,
Bütikofer P
.
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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 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.
Augustin,
The protein family of glucose transport facilitators: It's not only about glucose after all.
2010, Pubmed
Augustin,
The protein family of glucose transport facilitators: It's not only about glucose after all.
2010,
Pubmed
Batenburg,
Regulation and location of phosphatidylglycerol and phosphatidylinositol synthesis in type II cells isolated from fetal rat lung.
1985,
Pubmed
BLIGH,
A rapid method of total lipid extraction and purification.
1959,
Pubmed
Brun,
Cultivation and in vitro cloning or procyclic culture forms of Trypanosoma brucei in a semi-defined medium. Short communication.
1979,
Pubmed
Bütikofer,
'GPEET' procyclin is the major surface protein of procyclic culture forms of Trypanosoma brucei brucei strain 427.
1997,
Pubmed
Bütikofer,
Chlorpromazine inhibits vesiculation, alters phosphoinositide turnover and changes deformability of ATP-depleted RBCs.
1989,
Pubmed
Coady,
Identification of a novel Na+/myo-inositol cotransporter.
2002,
Pubmed
,
Xenbase
Cura,
Role of monosaccharide transport proteins in carbohydrate assimilation, distribution, metabolism, and homeostasis.
2012,
Pubmed
Di Daniel,
Evaluation of expression and function of the H+/myo-inositol transporter HMIT.
2009,
Pubmed
Drew,
Functional expression of a myo-inositol/H+ symporter from Leishmania donovani.
1995,
Pubmed
,
Xenbase
Einicker-Lamas,
Trypanosoma cruzi epimastigotes: regulation of myo-inositol transport by effectors of protein kinases A and C.
2007,
Pubmed
Einicker-Lamas,
Characterization of the myo-inositol transport system in Trypanosoma cruzi.
2000,
Pubmed
Fischl,
Phosphatidylinositol synthase from Saccharomyces cerevisiae. Reconstitution, characterization, and regulation of activity.
1986,
Pubmed
Flessner,
Similar [DE]XXXL[LI] motifs differentially target GLUT8 and GLUT12 in Chinese hamster ovary cells.
2009,
Pubmed
Gonzalez-Salgado,
myo-Inositol uptake is essential for bulk inositol phospholipid but not glycosylphosphatidylinositol synthesis in Trypanosoma brucei.
2012,
Pubmed
,
Xenbase
Hager,
Kinetics and specificity of the renal Na+/myo-inositol cotransporter expressed in Xenopus oocytes.
1995,
Pubmed
,
Xenbase
He,
Golgi duplication in Trypanosoma brucei.
2004,
Pubmed
Joost,
Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators.
2002,
Pubmed
Käll,
Advantages of combined transmembrane topology and signal peptide prediction--the Phobius web server.
2007,
Pubmed
Klamo,
Kinetics and stoichiometry of a proton/myo-inositol cotransporter.
1996,
Pubmed
,
Xenbase
Krogh,
Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes.
2001,
Pubmed
Leber,
Phospholipid-synthesizing enzymes in Golgi membranes of the yeast, Saccharomyces cerevisiae.
1995,
Pubmed
Lilley,
The essential roles of cytidine diphosphate-diacylglycerol synthase in bloodstream form Trypanosoma brucei.
2014,
Pubmed
Löfke,
Alternative metabolic fates of phosphatidylinositol produced by phosphatidylinositol synthase isoforms in Arabidopsis thaliana.
2008,
Pubmed
Macrae,
Plasmodium falciparum is dependent on de novo myo-inositol biosynthesis for assembly of GPI glycolipids and infectivity.
2014,
Pubmed
Martin,
Phosphatidylinositol synthesis is essential in bloodstream form Trypanosoma brucei.
2006,
Pubmed
Martin,
The glycosylphosphatidylinositol (GPI) biosynthetic pathway of bloodstream-form Trypanosoma brucei is dependent on the de novo synthesis of inositol.
2006,
Pubmed
Mayor,
Glycolipid precursors for the membrane anchor of Trypanosoma brucei variant surface glycoproteins. II. Lipid structures of phosphatidylinositol-specific phospholipase C sensitive and resistant glycolipids.
1990,
Pubmed
Michell,
Inositol lipids: from an archaeal origin to phosphatidylinositol 3,5-bisphosphate faults in human disease.
2013,
Pubmed
Mongan,
Substrate specificity of the Leishmania donovani myo-inositol transporter: critical role of inositol C-2, C-3 and C-5 hydroxyl groups.
2004,
Pubmed
Nikawa,
Phosphatidylinositol synthase from yeast.
1997,
Pubmed
Richmond,
Lipidomic analysis of bloodstream and procyclic form Trypanosoma brucei.
2010,
Pubmed
Schumann Burkard,
Genome-wide RNAi screens in bloodstream form trypanosomes identify drug transporters.
2011,
Pubmed
Serricchio,
Phosphatidylglycerophosphate synthase associates with a mitochondrial inner membrane complex and is essential for growth of Trypanosoma brucei.
2013,
Pubmed
Seyfang,
Four conserved cytoplasmic sequence motifs are important for transport function of the Leishmania inositol/H(+) symporter.
2000,
Pubmed
,
Xenbase
Seyfang,
Aspartate 19 and glutamate 121 are critical for transport function of the myo-inositol/H+ symporter from Leishmania donovani.
1997,
Pubmed
,
Xenbase
Shlomai,
The structure and replication of kinetoplast DNA.
2004,
Pubmed
Sutterwala,
Developmentally regulated sphingolipid synthesis in African trypanosomes.
2008,
Pubmed
Wirtz,
A tightly regulated inducible expression system for conditional gene knock-outs and dominant-negative genetics in Trypanosoma brucei.
1999,
Pubmed
Wright,
Biology of human sodium glucose transporters.
2011,
Pubmed
