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Sean Munro - One of the best experts on this subject based on the ideXlab platform.
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the saccharomyces cerevisiae protein mnn10p bed1p is a subunit of a golgi mannosyltransferase complex
Journal of Biological Chemistry, 1999Co-Authors: Joern Jungmann, Julian C Rayner, Sean MunroAbstract:Abstract In the yeast Saccharomyces cerevisiaemany of the N-linked glycans on cell wall and periplasmic proteins are modified by the addition of mannan, a large mannose-containing polysaccharide. Mannan comprises a backbone of approximately 50 α-1,6-linked mannoses to which are attached many branches consisting of α-1,2-linked and α-1,3-linked mannoses. The initiation and subsequent elongation of the mannan backbone is performed by two complexes of proteins in the cis Golgi. In this study we show that the product of theMNN10/BED1 gene is a component of one of these complexes, that which elongates the backbone. Analysis of interactions between the proteins in this complex shows that Mnn10p, and four previously characterized proteins (Anp1p, Mnn9p, Mnn11p, and Hoc1p) are indeed all components of the same large structure. Deletion of either Mnn10p, or its homologue Mnn11p, results in defects in mannan synthesisin vivo, and analysis of the enzymatic activity of the complexes isolated from mutant strains suggests that Mnn10p and Mnn11p are responsible for the majority of the α-1,6-polymerizing activity of the complex.
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Identification of the MNN2 and MNN5 mannosyltransferases required for forming and extending the mannose branches of the outer chain mannans of Saccharomyces cerevisiae
Journal of Biological Chemistry, 1998Co-Authors: Julian C Rayner, Sean MunroAbstract:The mannan structure found on the N-linked glycans of the yeast Saccharomyces cerevisiae is composed of a long backbone of alpha-1, 6-linked mannose to which are attached branches consisting of two alpha-1,2-linked mannoses followed by an alpha-1,3-linked mannose. In the mutants mnn2 and mnn5, the addition of the first and second of these two mannoses, respectively, is defective. In this paper, we report the identification of the genes corresponding to these mutations. The two genes encode closely related proteins with distant homology to the known Mnn1p alpha-1,3-mannosyltransferase. We show that these proteins are localized in an early compartment of the yeast Golgi and that they are not physically associated with each other or with the two protein complexes known to be involved in synthesizing the alpha-1,6-linked backbone. The identification of Mnn2p and Mnn5p allows us to assign Golgi proteins to all of the catalytic steps in S. cerevisiae mannan synthesis.
Andrew G Farr - One of the best experts on this subject based on the ideXlab platform.
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The major surface glycoprotein of Trypanosoma cruzi amastigotes are ligands of the human serum mannose-binding protein.
Infection and immunity, 1996Co-Authors: Stuart J. Kahn, Alejandro Aruffo, David Coder, Michael Wleklinski, R. A. B. Ezekowitz, Andrew G FarrAbstract:Trypanosoma cruzi, an obligate intracellular protozoan parasite, chronically infects mammals and causes Chagas' disease in humans. T. cruzi evasion of the mammalian immune response and establishment of chronic infection are poorly understood. During T. cruzi infection, amastigotes and trypomastigotes disseminate in the mammalian host and invade multiple cell types. Parasite surface carbohydrates and mammalian lectins have been implicated in the invasion of mammalian cells. A recent study has demonstrated that the human mannose-binding protein and the macrophage mannose receptor, two mammalian C-type lectins, bind to T. cruzi (S. J. Kahn, M. Wleklinski, A. Aruffo, A. Farr, D. Coder, and M. Kahn, J. Exp. Med. 182:1243-1258,1995). In this report we identify the major surface glycoproteins, including the SA85-1 glycoproteins, as T. cruzi ligands of the mannose-binding protein. Further characterization of the interaction between the mannose-binding protein and T. cruzi demonstrates that (i) the SA85-1 glycoproteins are expressed by amastigotes and trypomastigotes but only amastigotes express the mannose-binding protein ligand, (ii) treatment of amastigotes with alpha-mannosidase inhibits the binding of mannose-binding protein, and (iii) amastigote binding of mannose-binding protein is stable despite the spontaneous shedding of some glycoproteins from its surface. Together, the data indicate that developmentally regulated glycosylation of surface glycoproteins controls the expression of ligands that affect the interactions between T. cruzi and mannose-binding protein. It has been established that the binding of mannose-binding protein to microorganisms facilitates their uptake into phagocytic cells. Preferential opsonization of amastigotes with mannose-binding proteins may account for their clearance from the circulation and may contribute to the parasite's ability to invade different cell types.
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Trypanosoma cruzi amastigote adhesion to macrophages is facilitated by the mannose receptor.
Journal of Experimental Medicine, 1995Co-Authors: Stuart J. Kahn, Alejandro Aruffo, Andrew G Farr, David Coder, Michael Wleklinski, Maria KahnAbstract:Trypanosoma cruzi is an obligate intracellular protozoan parasite. The mammalian stage of the parasite life cycle describes amastigotes as an intracellular form that replicates, and trypomastigotes as an extracellular form that disseminates and invades cells. Recent studies, however, have demonstrated that amastigotes circulate in the blood of infected mammals and can invade mammalian cells. In this report, a T. cruzi surface glycoprotein gene, SA85-1.1, was expressed as an immunoglobulin chimera, and this recombinant globulin was used to screen normal mouse tissues for adhesive interactions. This approach identified a subset of macrophages in the skin and peripheral lymph node that bind the T. cruzi surface glycoproteins through the mannose receptor. To further examine the T. cruzi mannose receptor carbohydrate ligands, the interaction between T. cruzi and the mannose-binding protein, a mammalian lectin with similar carbohydrate binding specificities as the mannose receptor, was examined. These studies demonstrated that the mannose-binding protein recognized amastigotes, but not trypomastigotes or epimastigotes, and suggested that amastigotes would also be recognized by the mannose receptor. Therefore, amastigote adhesion to macrophages was investigated, and these experiments demonstrated that the mannose receptor contributes to amastigote adhesion. The data identify the first mammalian lectins that bind to T. cruzi, and are involved in T. cruzi invasion of mammalian cells. The data suggest that amastigotes and trypomastigotes may have developed different mechanisms to adhere to and invade host cells. In addition, it has been established that IFN-gamma-activated macrophages express low levels of the mannose receptor and are trypanocidal; this suggests that the interaction between amastigotes and the mannose receptor enables amastigotes to increase their adherence with a population of macrophages that are nontrypanocidal and permissive for their intracellular replication.
Andreas Conzelmann - One of the best experts on this subject based on the ideXlab platform.
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ethanolaminephosphate side chain added to glycosylphosphatidylinositol gpi anchor by mcd4p is required for ceramide remodeling and forward transport of gpi proteins from endoplasmic reticulum to golgi
Journal of Biological Chemistry, 2006Co-Authors: Christine Vionnet, Andreas ConzelmannAbstract:Abstract Glycosylphosphatidylinositol (GPI) anchors of mammals as well as yeast contain ethanolaminephosphate side chains on the α1–4- and the α1–6-linked mannoses of the anchor core structure (protein-CO-NH-(CH2)2-PO4-6Manα1–2Manα1–6Manα1–4GlcNH2-inositol-PO4-lipid). In yeast, the ethanolaminephosphate on the α1–4-linked mannose is added during the biosynthesis of the GPI lipid by Mcd4p. MCD4 is essential because Gpi10p, the mannosyltransferase adding the subsequent α1–2-linked mannose, requires substrates with an ethanolaminephosphate on the α1–4-linked mannose. The Gpi10p ortholog of Trypanosoma brucei has no such requirement. Here we show that the overexpression of this ortholog rescues mcd4Δ cells. Phenotypic analysis of the rescued mcd4Δ cells leads to the conclusion that the ethanolaminephosphate on the α1–4-linked mannose, beyond being an essential determinant for Gpi10p, is necessary for an efficient recognition of GPI lipids and GPI proteins by the GPI transamidase for the efficient transport of GPI-anchored proteins from the endoplasmic reticulum to Golgi and for the physiological incorporation of ceramides into GPI anchors by lipid remodeling. Furthermore, mcd4Δ cells have a marked defect in axial bud site selection, whereas this process is normal in gpi7Δ and gpi1. This also suggests that axial bud site selection specifically depends on the presence of the ethanolaminephosphate on the α1–4-linked mannose.
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ethanolaminephosphate side chain added to glycosylphosphatidylinositol gpi anchor by mcd4p is required for ceramide remodeling and forward transport of gpi proteins from endoplasmic reticulum to golgi
Journal of Biological Chemistry, 2006Co-Authors: Yonghua Zhu, Christine Vionnet, Andreas ConzelmannAbstract:Glycosylphosphatidylinositol (GPI) anchors of mammals as well as yeast contain ethanolaminephosphate side chains on the alpha1-4- and the alpha1-6-linked mannoses of the anchor core structure (protein-CO-NH-(CH(2))(2)-PO(4)-6Manalpha1-2Manalpha1-6Manalpha1-4GlcNH(2)-inositol-PO(4)-lipid). In yeast, the ethanolaminephosphate on the alpha1-4-linked mannose is added during the biosynthesis of the GPI lipid by Mcd4p. MCD4 is essential because Gpi10p, the mannosyltransferase adding the subsequent alpha1-2-linked mannose, requires substrates with an ethanolaminephosphate on the alpha1-4-linked mannose. The Gpi10p ortholog of Trypanosoma brucei has no such requirement. Here we show that the overexpression of this ortholog rescues mcd4Delta cells. Phenotypic analysis of the rescued mcd4Delta cells leads to the conclusion that the ethanolaminephosphate on the alpha1-4-linked mannose, beyond being an essential determinant for Gpi10p, is necessary for an efficient recognition of GPI lipids and GPI proteins by the GPI transamidase for the efficient transport of GPI-anchored proteins from the endoplasmic reticulum to Golgi and for the physiological incorporation of ceramides into GPI anchors by lipid remodeling. Furthermore, mcd4Delta cells have a marked defect in axial bud site selection, whereas this process is normal in gpi7Delta and gpi1. This also suggests that axial bud site selection specifically depends on the presence of the ethanolaminephosphate on the alpha1-4-linked mannose.
Stuart J. Kahn - One of the best experts on this subject based on the ideXlab platform.
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The major surface glycoprotein of Trypanosoma cruzi amastigotes are ligands of the human serum mannose-binding protein.
Infection and immunity, 1996Co-Authors: Stuart J. Kahn, Alejandro Aruffo, David Coder, Michael Wleklinski, R. A. B. Ezekowitz, Andrew G FarrAbstract:Trypanosoma cruzi, an obligate intracellular protozoan parasite, chronically infects mammals and causes Chagas' disease in humans. T. cruzi evasion of the mammalian immune response and establishment of chronic infection are poorly understood. During T. cruzi infection, amastigotes and trypomastigotes disseminate in the mammalian host and invade multiple cell types. Parasite surface carbohydrates and mammalian lectins have been implicated in the invasion of mammalian cells. A recent study has demonstrated that the human mannose-binding protein and the macrophage mannose receptor, two mammalian C-type lectins, bind to T. cruzi (S. J. Kahn, M. Wleklinski, A. Aruffo, A. Farr, D. Coder, and M. Kahn, J. Exp. Med. 182:1243-1258,1995). In this report we identify the major surface glycoproteins, including the SA85-1 glycoproteins, as T. cruzi ligands of the mannose-binding protein. Further characterization of the interaction between the mannose-binding protein and T. cruzi demonstrates that (i) the SA85-1 glycoproteins are expressed by amastigotes and trypomastigotes but only amastigotes express the mannose-binding protein ligand, (ii) treatment of amastigotes with alpha-mannosidase inhibits the binding of mannose-binding protein, and (iii) amastigote binding of mannose-binding protein is stable despite the spontaneous shedding of some glycoproteins from its surface. Together, the data indicate that developmentally regulated glycosylation of surface glycoproteins controls the expression of ligands that affect the interactions between T. cruzi and mannose-binding protein. It has been established that the binding of mannose-binding protein to microorganisms facilitates their uptake into phagocytic cells. Preferential opsonization of amastigotes with mannose-binding proteins may account for their clearance from the circulation and may contribute to the parasite's ability to invade different cell types.
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Trypanosoma cruzi amastigote adhesion to macrophages is facilitated by the mannose receptor.
Journal of Experimental Medicine, 1995Co-Authors: Stuart J. Kahn, Alejandro Aruffo, Andrew G Farr, David Coder, Michael Wleklinski, Maria KahnAbstract:Trypanosoma cruzi is an obligate intracellular protozoan parasite. The mammalian stage of the parasite life cycle describes amastigotes as an intracellular form that replicates, and trypomastigotes as an extracellular form that disseminates and invades cells. Recent studies, however, have demonstrated that amastigotes circulate in the blood of infected mammals and can invade mammalian cells. In this report, a T. cruzi surface glycoprotein gene, SA85-1.1, was expressed as an immunoglobulin chimera, and this recombinant globulin was used to screen normal mouse tissues for adhesive interactions. This approach identified a subset of macrophages in the skin and peripheral lymph node that bind the T. cruzi surface glycoproteins through the mannose receptor. To further examine the T. cruzi mannose receptor carbohydrate ligands, the interaction between T. cruzi and the mannose-binding protein, a mammalian lectin with similar carbohydrate binding specificities as the mannose receptor, was examined. These studies demonstrated that the mannose-binding protein recognized amastigotes, but not trypomastigotes or epimastigotes, and suggested that amastigotes would also be recognized by the mannose receptor. Therefore, amastigote adhesion to macrophages was investigated, and these experiments demonstrated that the mannose receptor contributes to amastigote adhesion. The data identify the first mammalian lectins that bind to T. cruzi, and are involved in T. cruzi invasion of mammalian cells. The data suggest that amastigotes and trypomastigotes may have developed different mechanisms to adhere to and invade host cells. In addition, it has been established that IFN-gamma-activated macrophages express low levels of the mannose receptor and are trypanocidal; this suggests that the interaction between amastigotes and the mannose receptor enables amastigotes to increase their adherence with a population of macrophages that are nontrypanocidal and permissive for their intracellular replication.
Julian C Rayner - One of the best experts on this subject based on the ideXlab platform.
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the saccharomyces cerevisiae protein mnn10p bed1p is a subunit of a golgi mannosyltransferase complex
Journal of Biological Chemistry, 1999Co-Authors: Joern Jungmann, Julian C Rayner, Sean MunroAbstract:Abstract In the yeast Saccharomyces cerevisiaemany of the N-linked glycans on cell wall and periplasmic proteins are modified by the addition of mannan, a large mannose-containing polysaccharide. Mannan comprises a backbone of approximately 50 α-1,6-linked mannoses to which are attached many branches consisting of α-1,2-linked and α-1,3-linked mannoses. The initiation and subsequent elongation of the mannan backbone is performed by two complexes of proteins in the cis Golgi. In this study we show that the product of theMNN10/BED1 gene is a component of one of these complexes, that which elongates the backbone. Analysis of interactions between the proteins in this complex shows that Mnn10p, and four previously characterized proteins (Anp1p, Mnn9p, Mnn11p, and Hoc1p) are indeed all components of the same large structure. Deletion of either Mnn10p, or its homologue Mnn11p, results in defects in mannan synthesisin vivo, and analysis of the enzymatic activity of the complexes isolated from mutant strains suggests that Mnn10p and Mnn11p are responsible for the majority of the α-1,6-polymerizing activity of the complex.
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Identification of the MNN2 and MNN5 mannosyltransferases required for forming and extending the mannose branches of the outer chain mannans of Saccharomyces cerevisiae
Journal of Biological Chemistry, 1998Co-Authors: Julian C Rayner, Sean MunroAbstract:The mannan structure found on the N-linked glycans of the yeast Saccharomyces cerevisiae is composed of a long backbone of alpha-1, 6-linked mannose to which are attached branches consisting of two alpha-1,2-linked mannoses followed by an alpha-1,3-linked mannose. In the mutants mnn2 and mnn5, the addition of the first and second of these two mannoses, respectively, is defective. In this paper, we report the identification of the genes corresponding to these mutations. The two genes encode closely related proteins with distant homology to the known Mnn1p alpha-1,3-mannosyltransferase. We show that these proteins are localized in an early compartment of the yeast Golgi and that they are not physically associated with each other or with the two protein complexes known to be involved in synthesizing the alpha-1,6-linked backbone. The identification of Mnn2p and Mnn5p allows us to assign Golgi proteins to all of the catalytic steps in S. cerevisiae mannan synthesis.
