Trypanosoma brucei Bloodstream Forms Depend upon Uptake of myo-Inositol for Golgi Complex Phosphatidylinositol Synthesis and Normal Cell Growth
Data(s) |
01/06/2015
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Resumo |
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. |
Formato |
application/pdf |
Identificador |
http://boris.unibe.ch/76346/1/B%C3%BCtikofer%20Trypanosoma%20brucei%20Bloodstream.pdf González Salgado, Amaia; Steinmann, Michael Eduard; Major, Louise L; Sigel, Erwin; Reymond, Jean-Louis; Smith, Terry K; Bütikofer, Peter (2015). Trypanosoma brucei Bloodstream Forms Depend upon Uptake of myo-Inositol for Golgi Complex Phosphatidylinositol Synthesis and Normal Cell Growth. Eukaryotic cell, 14(6), pp. 616-624. American Society for Microbiology ASM 10.1128/EC.00038-15 <http://dx.doi.org/10.1128/EC.00038-15> doi:10.7892/boris.76346 info:doi:10.1128/EC.00038-15 info:pmid:25888554 urn:issn:1535-9778 |
Idioma(s) |
eng |
Publicador |
American Society for Microbiology ASM |
Relação |
http://boris.unibe.ch/76346/ |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
González Salgado, Amaia; Steinmann, Michael Eduard; Major, Louise L; Sigel, Erwin; Reymond, Jean-Louis; Smith, Terry K; Bütikofer, Peter (2015). Trypanosoma brucei Bloodstream Forms Depend upon Uptake of myo-Inositol for Golgi Complex Phosphatidylinositol Synthesis and Normal Cell Growth. Eukaryotic cell, 14(6), pp. 616-624. American Society for Microbiology ASM 10.1128/EC.00038-15 <http://dx.doi.org/10.1128/EC.00038-15> |
Palavras-Chave | #570 Life sciences; biology #610 Medicine & health #540 Chemistry |
Tipo |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion PeerReviewed |