The major surface antigens of Entamoeba histolytica trophozoites are GPI-anchored proteophosphoglycans

Moody-Haupt, Sue; Patterson, Joshua T.; Mirelman, David; McConville, Malcolm J.

doi:10.1006/jmbi.2000.3577

Cited by 105 publications

(77 citation statements)

References 25 publications

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“…Among the previously described glycoconjugates of Eh are the serinerich protein terminal O-linked N-acetylglucosamine (5) and a glycosylphosphatidylinositol-anchored proteophosphoglycan with an acidic polypeptide to which probably a polymer containing glucose and galactose is attached via a serine phosphate (4). It is tempting to hypothesize that the above-described transporters for UDP-galactose and UDP-glucose of the GA-like vesicles play a role in the biosynthesis of this polymer.…”

Section: Discussionmentioning

confidence: 99%

Golgi and Endoplasmic Reticulum Functions Take Place in Different Subcellular Compartments of Entamoeba histolytica

Bredeston

Caffaro

Samuelson

et al. 2005

Journal of Biological Chemistry

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Entamoeba histolytica is a protozoan parasite that causes dysentery in developing countries of Africa, Asia, and Latin America. The lack of a defined Golgi apparatus in E. histolytica as well as in other protists led to the hypothesis that they had evolved prior to the acquisition of such organelle even though glycoproteins, glycolipids, and antigens have been detected, the latter of which react with antibodies against Golgi apparatus proteins of higher eukaryotes. We here provide direct evidence for Golgi apparatus-like functions in E. histolytica as well as for components of glycoprotein folding quality control. Using a combination of bioinformatic, cell biological, and biochemical approaches we have (a) cloned and expressed the E. histolytica UDP-galactose transporter in Saccharomyces cerevisiae; its K m for UDP-galactose is 2.9 M; (b) characterized vesicles in an extract of the above protist, which transport UDPgalactose into their lumen with a K m of 2.7 M; (c) detected galactosyltransferase activity(ies) in the lumen of the above vesicles with the K m for UDP-galactose, using endogenous acceptors, being 93 M; (d) measured latent apyrase activities in the above vesicles, suggesting they are in the lumen; (e) characterized UDP-glucose transport activities in Golgi apparatus and endoplasmic reticulum-like vesicles with K m s for UDP-glucose of ϳ2-4 M. Although the endoplasmic reticulum-like fraction showed UDP-glucose: glycoprotein glucosyltransferase activity, the Golgi apparatus-like fraction did not. This fraction contained other glucosyltransferases. Together, these studies demonstrate that E. histolytica has different vesicles that play a role in protein glycosylation and folding quality control, analogous to the above organellar functions of higher eukaryotes.

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Section: Discussionmentioning

confidence: 99%

Golgi and Endoplasmic Reticulum Functions Take Place in Different Subcellular Compartments of Entamoeba histolytica

Bredeston

Caffaro

Samuelson

et al. 2005

Journal of Biological Chemistry

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“…(153). Protein phosphoglycosylation has not been identified in any metazoan organisms to date, although there is increasing evidence that this type of modification (often involving different sugar-phosphate linkages) may be common in other unicellular eukaryotes, such as Dictyostelium discoideum and the protozoan parasite Entamoeba histolytica (137,219).…”

Section: Protein Phosphoglycosylationmentioning

confidence: 99%

Secretory Pathway of Trypanosomatid Parasites

McConville

Mullin

Ilgoutz

et al. 2002

Microbiol Mol Biol Rev

222

191

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The Trypanosomatidae comprise a large group of parasitic protozoa, some of which cause important diseases in humans. These include Trypanosoma brucei (the causative agent of African sleeping sickness and nagana in cattle), Trypanosoma cruzi (the causative agent of Chagas' disease in Central and South America), and Leishmania spp. (the causative agent of visceral and [muco]cutaneous leishmaniasis throughout the tropics and subtropics). The cell surfaces of these parasites are covered in complex protein- or carbohydrate-rich coats that are required for parasite survival and infectivity in their respective insect vectors and mammalian hosts. These molecules are assembled in the secretory pathway. Recent advances in the genetic manipulation of these parasites as well as progress with the parasite genome projects has greatly advanced our understanding of processes that underlie secretory transport in trypanosomatids. This article provides an overview of the organization of the trypanosomatid secretory pathway and connections that exist with endocytic organelles and multiple lytic and storage vacuoles. A number of the molecular components that are required for vesicular transport have been identified, as have some of the sorting signals that direct proteins to the cell surface or organelles in the endosome-vacuole system. Finally, the subcellular organization of the major glycosylation pathways in these parasites is reviewed. Studies on these highly divergent eukaryotes provide important insights into the molecular processes underlying secretory transport that arose very early in eukaryotic evolution. They also reveal unusual or novel aspects of secretory transport and protein glycosylation that may be exploited in developing new antiparasite drugs

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“…They may also exist in the T. brucei gp72 homologue Fla-1 (77). The occurrence of P-linked glycans in nature is highly restricted and, outside the trypanosomatids, has been reported as occurring only in Dictyostelium (108) and Entamoeba (70). Whereas the phosphosaccharides of NETNES are composed of mannose chains only, those of gp72 are extremely complex, containing ␣-L-Fuc, ␣-L-Rha, and ␤-D-Xyl as well as GlcNAc, Galp, and Galf (3,31,40).…”

mentioning

confidence: 99%

Sugar Nucleotide Pools of Trypanosoma brucei , Trypanosoma cruzi , and Leishmania major

2007

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The cell surface glycoconjugates of trypanosomatid parasites are intimately involved in parasite survival, infectivity, and virulence in their insect vectors and mammalian hosts. Although there is a considerable body of work describing their structure, biosynthesis, and function, little is known about the sugar nucleotide pools that fuel their biosynthesis. In order to identify and quantify parasite sugar nucleotides, we developed an analytical method based on liquid chromatography-electrospray ionization-tandem mass spectrometry using multiple reaction monitoring. This method was applied to the bloodstream and procyclic forms of Trypanosoma brucei, the epimastigote form of T. cruzi, and the promastigote form of Leishmania major. The trypanosomatids are protozoan parasites that impose a major health burden on many countries in the developing world, causing a wide range of diseases over three continents. Like most eukaryotes, the cell surfaces and endosomal/lysosomal systems of these organisms are rich in glycoconjugates, some of which play essential roles in their survival, infectivity, or virulence. The glycoconjugate repertoires of the three trypanosomatids studied here, Trypanosoma brucei, T. cruzi, and Leishmania major, are fundamentally different, reflecting their disparate life cycles, modes of infection, and disease pathologies (see references 5,27,28,38,47,65, and 69 and references therein). The monosaccharides that make up these glycoconjugates vary between the three trypanosomatid species. For example, all three contain D-mannose (Man), D-Nacetylglucosamine (GlcNAc), D-glucosamine (GlcN), D-glucose (Glc), and D-galactopyranose (Galp), while only T. cruzi and L. major contain D-galactofuranose (Galf), only T. cruzi contains D-xylose (Xyl), L-rhamnopyranose (Rha), and L-fucose (Fuc), and only L. major contains D-arabinopyranose (Ara) ( Table 1). However, a unifying theme of their glycobiology is an abundance of cell surface glycosylphosphatidylinositol (GPI)-anchored glycoproteins and/or non-proteinlinked GPI structures.The protein-linked GPI glycans of the leishmania are the simplest in structure, consisting of the conserved Man␣1-2Man␣1-6Man␣1-4GlcN core. Those of T. cruzi are principally Man␣1-2Man␣1-2Man␣1-6Man␣1-4GlcN, and those of T. brucei are the most complex, with ␣-D-Galp and ␤-D-Galp side chains in the bloodstream form and sialylated poly-N-acetyllactosamine (poly-LacNAc) side chains in the procyclic form (27).The non-protein-linked GPI structures include the so-called glycoinositolphospholipids, or GIPLs, that are most abundant in the leishmania and T. cruzi species (58, 64, 90) but are also found in procyclic-form T. brucei (60,73,122) and bloodstream form T. brucei (39,63). Non-protein-linked GPIs also include the more exotic leishmania-specific lipophosphoglycan (LPG) structures (38,47,64,65). The leishmania LPGs contain characteristic phosphosaccharide repeats of Galp␤1-4Man␣1-P, which in L. major can have ␤-D-Galp and ␣-D-Arap side chains (66,67). These repeats are also found in the secr...

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The major surface antigens of Entamoeba histolytica trophozoites are GPI-anchored proteophosphoglycans

Cited by 105 publications

References 25 publications

Golgi and Endoplasmic Reticulum Functions Take Place in Different Subcellular Compartments of Entamoeba histolytica

Golgi and Endoplasmic Reticulum Functions Take Place in Different Subcellular Compartments of Entamoeba histolytica

Secretory Pathway of Trypanosomatid Parasites

Sugar Nucleotide Pools of Trypanosoma brucei , Trypanosoma cruzi , and Leishmania major

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