Files in this item
Trypanosoma brucei bloodstream forms depend upon uptake of myo-inositol for Golgi phosphatidylinositol synthesis and normal cell growth
Item metadata
dc.contributor.author | González-Salgado, Amaia | |
dc.contributor.author | Steinmann, Michael | |
dc.contributor.author | Major, Louise Laura | |
dc.contributor.author | Sigel, Erwin | |
dc.contributor.author | Reymond, Jean-Louis | |
dc.contributor.author | Smith, Terry K | |
dc.contributor.author | Bütikofer, Peter | |
dc.date.accessioned | 2016-08-02T14:30:06Z | |
dc.date.available | 2016-08-02T14:30:06Z | |
dc.date.issued | 2015-06 | |
dc.identifier | 194620111 | |
dc.identifier | c2c5814c-c4cc-4622-85d2-716cbc382f8d | |
dc.identifier | 84930398943 | |
dc.identifier | 000355543000010 | |
dc.identifier.citation | 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 . https://doi.org/10.1128/EC.00038-15 | en |
dc.identifier.issn | 1535-9778 | |
dc.identifier.other | ORCID: /0000-0001-5287-4488/work/51010275 | |
dc.identifier.uri | https://hdl.handle.net/10023/9245 | |
dc.description.abstract | 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. | |
dc.format.extent | 1168426 | |
dc.language.iso | eng | |
dc.relation.ispartof | Eukaryotic Cell | en |
dc.subject | QH301 Biology | en |
dc.subject | SDG 3 - Good Health and Well-being | en |
dc.subject.lcc | QH301 | en |
dc.title | Trypanosoma brucei bloodstream forms depend upon uptake of myo-inositol for Golgi phosphatidylinositol synthesis and normal cell growth | en |
dc.type | Journal article | en |
dc.contributor.sponsor | The Wellcome Trust | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.identifier.doi | 10.1128/EC.00038-15 | |
dc.description.status | Peer reviewed | en |
dc.identifier.grantnumber | 093228/Z/10/Z | en |
This item appears in the following Collection(s)
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.