ArticleThe EMBO journal1995
The role of inositol acylation and inositol deacylation in GPI biosynthesis in Trypanosoma brucei.
Article in The EMBO journal, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 106 citations in OpenAlex.
- Identification of the glycosylphosphatidylinositol-specific phospholipase A2 (GPI-PLA2) that mediates GPI fatty acid remodeling in Trypanosoma brucei.The Journal of biological chemistry · 2023Article
- Article
- Genome-wide CRISPR screen reveals CLPTM1L as a lipid scramblase required for efficient glycosylphosphatidylinositol biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Identification of TbPBN1 in Trypanosoma brucei reveals a conserved heterodimeric architecture for glycosylphosphatidylinositol-mannosyltransferase-I.Molecular microbiology · 2022Article
- Article
- The Glycosylphosphatidylinositol Anchor: A Linchpin for Cell Surface Versatility of Trypanosomatids.Frontiers in cell and developmental biology · 2021Review
- Transcriptome Remodeling in Trypanosoma cruzi and Human Cells during Intracellular Infection.PLoS pathogens · 2016Article
- Biosynthesis of GPI-anchored proteins: special emphasis on GPI lipid remodeling.Journal of lipid research · 2016Review
- Probing the substrate specificity of Trypanosoma brucei GlcNAc-PI de-N-acetylase with synthetic substrate analogues.Organic & biomolecular chemistry · 2014Article
- Recent progress in synthetic and biological studies of GPI anchors and GPI-anchored proteins.Current opinion in chemical biology · 2013Review
- Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway.PLoS neglected tropical diseases · 2013Article
- Comparative SILAC proteomic analysis of Trypanosoma brucei bloodstream and procyclic lifecycle stages.PloS one · 2012Article
- Synthesis of potential metal-binding group compounds to examine the zinc dependency of the GPI de-N-acetylase metalloenzyme in Trypanosoma brucei.Carbohydrate research · 2011Article
- Lipid metabolism in Trypanosoma brucei.Molecular and biochemical parasitology · 2010Review
- Trypanosome glycosylphosphatidylinositol biosynthesis.The Korean journal of parasitology · 2009Review
- Yeast ARV1 is required for efficient delivery of an early GPI intermediate to the first mannosyltransferase during GPI assembly and controls lipid flow from the endoplasmic reticulum.Molecular biology of the cell · 2008Article
- GPI-anchored proteins and free GPI glycolipids of procyclic form Trypanosoma brucei are nonessential for growth, are required for colonization of the tsetse fly, and are not the only components of the surface coat.Molecular biology of the cell · 2006Article
- Membrane topology and transient acylation of Toxoplasma gondii glycosylphosphatidylinositols.Eukaryotic cell · 2006Article
- The glycosylphosphatidylinositol (GPI) biosynthetic pathway of bloodstream-form Trypanosoma brucei is dependent on the de novo synthesis of inositol.Molecular microbiology · 2006Article
- Phosphatidylinositol synthesis is essential in bloodstream form Trypanosoma brucei.The Biochemical journal · 2006Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
The compound diisopropylfluorophosphate (DFP) selectively inhibits an inositol deacylase activity in living trypanosomes that, together with the previously described phenylmethylsulfonyl fluoride (PMSF)-sensitive inositol acyltransferase, maintains a dynamic equilibrium between the glycosylphosphatidylinositol (GPI) anchor precursor, glycolipid A [NH2(CH2)2PO4-6Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6myo-inositol-1-PO4-sn-1,2-dimyristoylglycerol], and its inositol acylated form, glycolipid C. Experiments using DFP in living trypanosomes and a trypanosome cell-free system suggest that earlier GPI intermediates are also in equilibrium between their inositol acylated and nonacylated forms. However, unlike mammalian and yeast cells, bloodstream form trypanosomes do not appear to produce an inositol acylated form of glucosaminylphosphatidylinositol (GlcN-PI). A specific function of inositol acylation in trypanosomes may be to enhance the efficiency of ethanolamine phosphate addition to the Man3GlcN-(acyl)PI intermediate. Inositol deacylation appears to be a prerequisite for fatty acid remodelling of GPI intermediates that leads to the exclusive presence of myristic acid in glycolipid A and, ultimately, in the variant surface glycoprotein (VSG). In the presence of DFP, the de novo synthesis of GPI precursors cannot proceed beyond glycolipid C' (the unremodelled version of glycolipid C) and lyso-glycolipid C'. Under these conditions glycolipid C'-type GPI anchors appear on newly synthesized VSG molecules. However, the efficiencies of both anchor addition to VSG and N-glycosylation of VSG were significantly reduced. A modified model of the GPI biosynthetic pathway in bloodstream form African trypanosomes incorporating these findings is presented.
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