Glycosyl-Phosphatidylinositol Moiety That Anchors
            <i>Trypanosoma brucei</i>
            Variant Surface Glycoprotein to the Membrane

Ferguson, Michael A. J.; Homans, Steve W.; Dwek, Raymond A.; Rademacher, Thomas W.

doi:10.1126/science.3340856

Cited by 736 publications

(392 citation statements)

References 44 publications

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“…The acylation and glycosylation of GYMSSA is therefore consistent with the location on the merozoite surface membrane indicated by immunofluorescence. The variant surface glycoprotein of African trypanosomes contains myristilated phosphatidyl inositol linked to the C terminus ofthe protein through carbohydrate (24). The myristic acid is believed to anchor the trypanosome protein to the membrane in a manner readily reversed by the action of phosphatidyl inositol specific phospholipase C. The myristic acid in GYMSSA may serve a similar function in anchoring the protein to the merozoite membrane in a manner that permits rapid cleavage from the membrane during invasion.…”

Section: Discussionmentioning

confidence: 99%

Studies on glycoproteins in the human malaria parasite Plasmodium falciparum. Identification of a myristilated 45kDa merozoite membrane glycoprotein

Ramasamy

1987

Immunol Cell Biol

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Section: Discussionmentioning

confidence: 99%

Studies on glycoproteins in the human malaria parasite Plasmodium falciparum. Identification of a myristilated 45kDa merozoite membrane glycoprotein

Ramasamy

1987

Immunol Cell Biol

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“…In T. brucei where GPI-PLCp is endogenous (18,20,57), each cell contains ϳ10 7 molecules of VSG, a GPI-anchored protein (63). How does T. brucei retain sufficient GPIs needed for anchoring VSG to the plasma membrane when GPI-PLCp is present in the same cell?…”

Section: Discussionmentioning

confidence: 99%

Endosomes, Glycosomes, and Glycosylphosphatidylinositol Catabolism in Leishmania major

Zheng

Butler

Tweten

et al. 2004

Journal of Biological Chemistry

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Glycosylphosphatidylinositols (GPIs) serve as membrane anchors of polysaccharides and proteins in the protozoan parasite Leishmania major. Free GPIs that are not attached to macromolecules are present in L. major as intermediates of protein-GPI and polysaccharide-GPI synthesis or as terminal glycolipids. The importance of the intracellular location of GPIs in vivo for functions of the glycolipids is not appreciated. To examine the roles of intracellular free GPI pools for attachment to polypeptide, a GPI-specific phospholipase C (GPI-PLCp) from Trypanosoma brucei was used to probe trafficking of GPI pools inside L. major. The locations of GPIs were determined, and their catabolism by GPI-PLCp was analyzed with respect to the intracellular location of the enzyme. GPIs accumulated on the endo-lysosomal system, where GPI-PLCp was also de- tected. A peptide motif [CS][CS]-x(0,2)-G-x(1)-C-x(2,3)-Sx(3)-L formed part of an endosome targeting signal for GPI-PLCp. Mutations of the endosome targeting motif caused GPI-PLCp to associate with glycosomes (peroxisomes). Endosomal GPI-PLCp caused a deficiency of protein-GPI in L. major, whereas glycosomal GPI-PLCp failed to produce the GPI deficiency. We surmise that (i) endo-lysosomal GPIs are important for biogenesis of GPI-anchored proteins in L. major; (ii) sequestration of GPI-PLCp to glycosomes protects free protein-GPIs from cleavage by the phospholipase. In T. brucei, protein-GPIs are concentrated at the endoplasmic reticulum, separated from GPI-PLCp. These observations support a model in which glycosome sequestration of a catabolic GPI-PLCp preserves free protein-GPIs in vivo.

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“…B, microsomes from strain 521-17A-H42 were labeled with UDP-[ 3 H]GlcNAc and lipid 4c was purified by preparative TLC. The labeled head group of lipid 4c was isolated, treated or not with JBAM, an exomannosidase without any linkage specificity, followed by treatment with HF at 0°C to specifically cleave phosphodiesters and finally N-acetylated (NAc) using published methods (48). The generated fragments were analyzed by paper chromatography along with radiolabeled Man 0 -4 -GlcNAcIns standards.…”

Section: Addition Of Ethanolamine Phosphate To Man1mentioning

confidence: 99%

Glycosylphosphatidylinositol (GPI) Proteins of Saccharomyces cerevisiae Contain Ethanolamine Phosphate Groups on the α1,4-linked Mannose of the GPI Anchor

Imhof¹,

Flury²,

Vionnet

et al. 2004

Journal of Biological Chemistry

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In humans and Saccharomyces cerevisiae the free glycosylphosphatidylinositol (GPI) lipid precursor contains several ethanolamine phosphate side chains, but these side chains had been found on the protein-bound GPI anchors only in humans, not yeast. Here we confirm that the ethanolamine phosphate side chain added by Mcd4p to the first mannose is a prerequisite for the addition of the third mannose to the GPI precursor lipid and demonstrate that, contrary to an earlier report, an ethanolamine phosphate can equally be found on the majority of yeast GPI protein anchors. Curiously, the stability of this substituent during preparation of anchors is much greater in gpi7⌬ sec18 double mutants than in either single mutant or wild type cells, indicating that the lack of a substituent on the second mannose (caused by the deletion of GPI7) influences the stability of the one on the first mannose. The phosphodiesterlinked substituent on the second mannose, probably a further ethanolamine phosphate, is added to GPI lipids by endoplasmic reticulum-derived microsomes in vitro but cannot be detected on GPI proteins of wild type cells and undergoes spontaneous hydrolysis in saline. Genetic manipulations to increase phosphatidylethanolamine levels in gpi7⌬ cells by overexpression of PSD1 restore cell growth at 37°C without restoring the addition of a substituent to Man2. The three putative ethanolamine-phosphate transferases Gpi13p, Gpi7p, and Mcd4p cannot replace each other even when overexpressed. Various models trying to explain how Gpi7p, a plasma membrane protein, directs the addition of ethanolamine phosphate to mannose 2 of the GPI core have been formulated and put to the test.

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Glycosyl-Phosphatidylinositol Moiety That Anchors Trypanosoma brucei Variant Surface Glycoprotein to the Membrane

Cited by 736 publications

References 44 publications

Studies on glycoproteins in the human malaria parasite Plasmodium falciparum. Identification of a myristilated 45kDa merozoite membrane glycoprotein

Studies on glycoproteins in the human malaria parasite Plasmodium falciparum. Identification of a myristilated 45kDa merozoite membrane glycoprotein

Endosomes, Glycosomes, and Glycosylphosphatidylinositol Catabolism in Leishmania major

Glycosylphosphatidylinositol (GPI) Proteins of Saccharomyces cerevisiae Contain Ethanolamine Phosphate Groups on the α1,4-linked Mannose of the GPI Anchor

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