Genomes and Genes
dolichol monophosphate mannose
Summary: A lipophilic glycosyl carrier of the monosaccharide mannose in the biosynthesis of oligosaccharide phospholipids and glycoproteins.
- Lefeber D, Schönberger J, Morava E, Guillard M, Huyben K, Verrijp K, et al. Deficiency of Dol-P-Man synthase subunit DPM3 bridges the congenital disorders of glycosylation with the dystroglycanopathies. Am J Hum Genet. 2009;85:76-86 pubmed publisher..This mild Dol-P-Man biosynthesis defect due to DPM3 mutations is a cause for alpha-dystroglycanopathy, thereby bridging the congenital disorders of glycosylation with the dystroglycanopathies. ..
- Rush J, Gao N, Lehrman M, Matveev S, Waechter C. Suppression of Rft1 expression does not impair the transbilayer movement of Man5GlcNAc2-P-P-dolichol in sealed microsomes from yeast. J Biol Chem. 2009;284:19835-42 pubmed publisher..All of these results indicate that although Rft1 may play a critical role in vivo, depletion of this protein does not impair the transbilayer movement of M5-DLO in sealed microsomal fractions prepared from disrupted cells...
- Korner C, Lehle L, Von Figura K. Abnormal synthesis of mannose 1-phosphate derived carbohydrates in carbohydrate-deficient glycoprotein syndrome type I fibroblasts with phosphomannomutase deficiency. Glycobiology. 1998;8:165-71 pubmed..As a consequence, truncated oligosaccharides were transferred to newly synthesized glycoproteins. The metabolic changes can be explained by a deficiency of phosphomannomutase activity, which was reduced to </=10% of control. ..
- D SOUZA SCHOREY C, McLachlan K, Krag S, Elbein A. Mammalian glycosyltransferases prefer glycosyl phosphoryl dolichols rather than glycosyl phosphoryl polyprenols as substrates for oligosaccharyl synthesis. Arch Biochem Biophys. 1994;308:497-503 pubmed..These findings are significant in terms of understanding the glycosylation phenotypes of Chinese hamster ovary cell mutants of the Lec9 complementation group, which lack the ability to convert polyprenol into dolichol. ..
- Kabakoff B, Doyle J, Kandutsch A. Relationships among dolichyl phosphate, glycoprotein synthesis, and cell culture growth. Arch Biochem Biophys. 1990;276:382-9 pubmed..The results suggest that the rate of cell culture growth may be influenced by the level of dolichyl phosphate acting to limit the synthesis of N-linked glycoproteins. ..
- Beck P, Gething M, Sambrook J, Lehrman M. Complementing mutant alleles define three loci involved in mannosylation of Man5-GlcNAc2-P-P-dolichol in Chinese hamster ovary cells. Somat Cell Mol Genet. 1990;16:539-48 pubmed..One mutation affects mannose-P-dolichol biosynthesis (Lec15), three affect dolichol phosphate biosynthesis (Lec9), and three appear to affect the functional orientation of enzyme substrates (PIR). ..
- Duvet S, Op De Beeck A, Cocquerel L, Wychowski C, Cacan R, Dubuisson J. Glycosylation of the hepatitis C virus envelope protein E1 occurs posttranslationally in a mannosylphosphoryldolichol-deficient CHO mutant cell line. Glycobiology. 2002;12:95-101 pubmed..Comparisons with the N-glycosylation of other proteins expressed in B3F7 cells indicate that the posttranslational glycosylation of E1 is likely due to specific folding features of this acceptor protein. ..
- Brown J, Guther M, Field R, Ferguson M. Hydrophobic mannosides act as acceptors for trypanosome alpha-mannosyltransferases. Glycobiology. 1997;7:549-58 pubmed..One of the compounds, Man alpha 1-6 Man alpha 1-O-(CH2)7CH3, inhibited endogenous GPI biosynthesis in the cell-free system, suggesting that it could be a substrate for the trypanosome Dol-P-Man:Man2GlcN-Pl alpha 1-2 mannosyltransferase. ..
- Doucey M, Hess D, Cacan R, Hofsteenge J. Protein C-mannosylation is enzyme-catalysed and uses dolichyl-phosphate-mannose as a precursor. Mol Biol Cell. 1998;9:291-300 pubmed..It is concluded that a microsomal transferase catalyses C-mannosylation of Trp-7, and that the minimal biosynthetic pathway can be defined as: Man -> -> GDP-Man -> Dol-P-Man -> (C2-Man-)Trp. ..
- Adamany A, Spiro R. Glycoprotein biosynthesis: studies on thyroid mannosyltransferases. II. Characterization of a polyisoprenyl mannosyl phosphate and evaluation of its intermediary role in the glycosylation of exogenous acceptors. J Biol Chem. 1975;250:2842-54 pubmed
- Rush J, Waechter C. Transmembrane movement of a water-soluble analogue of mannosylphosphoryldolichol is mediated by an endoplasmic reticulum protein. J Cell Biol. 1995;130:529-36 pubmed..It is possible that the same membrane protein(s) participates in the transbilayer movement of Man-P-Dol in the ER. ..
- Runge K, Robbins P. A new yeast mutation in the glucosylation steps of the asparagine-linked glycosylation pathway. Formation of a novel asparagine-linked oligosaccharide containing two glucose residues. J Biol Chem. 1986;261:15582-90 pubmed
- Tartakoff A, Singh N. How to make a glycoinositol phospholipid anchor. Trends Biochem Sci. 1992;17:470-3 pubmed..Mutations that interrupt this path are, remarkably, compatible with survival of cells in culture, but are associated with at least one human disease. ..
- Sharma C, Kaushal G, Pan Y, Elbein A. Purification and characterization of dolichyl-P-mannose:Man5(GlcNAc)2-PP-dolichol mannosyltransferase. Biochemistry. 1990;29:8901-7 pubmed..This linkage was further confirmed by acetolysis of the oligosaccharide product [i.e., Man6(GlcNAc)2], which gave a labeled disaccharide as the major product (greater than 90%). ..
- Menon A, Mayor S, Schwarz R. Biosynthesis of glycosyl-phosphatidylinositol lipids in Trypanosoma brucei: involvement of mannosyl-phosphoryldolichol as the mannose donor. EMBO J. 1990;9:4249-58 pubmed..In this paper we use these preparations to show that all three mannose residues in the glycosyl-phosphatidylinositol glycan are derived from dolichol-P-mannose. ..
- Menon A, Schwarz R, Mayor S, Cross G. Cell-free synthesis of glycosyl-phosphatidylinositol precursors for the glycolipid membrane anchor of Trypanosoma brucei variant surface glycoproteins. Structural characterization of putative biosynthetic intermediates. J Biol Chem. 1990;265:9033-42 pubmed..Structural analyses of these putative biosynthetic intermediates suggest that glycolipid assembly occurs via the sequential glycosylation of phosphatidylinositol. ..
- Cacan R, Villers C, Belard M, Kaiden A, Krag S, Verbert A. Different fates of the oligosaccharide moieties of lipid intermediates. Glycobiology. 1992;2:127-36 pubmed..The other metabolic fate of non-glucosylated oligosaccharide-lipids, glucosylation, results in their use as effective substrates for the glycosylation of proteins or in the generation of neutral oligosaccharides...
- Tomita S, Inoue N, Maeda Y, Ohishi K, Takeda J, Kinoshita T. A homologue of Saccharomyces cerevisiae Dpm1p is not sufficient for synthesis of dolichol-phosphate-mannose in mammalian cells. J Biol Chem. 1998;273:9249-54 pubmed..Therefore, in contrast to yeast, mammalian cells require hDPM1/mDPM1 protein and a product of another gene that is defective in Lec15 mutant cells for synthesis of Dol-P-Man. ..
- Garami A, Mehlert A, Ilg T. Glycosylation defects and virulence phenotypes of Leishmania mexicana phosphomannomutase and dolicholphosphate-mannose synthase gene deletion mutants. Mol Cell Biol. 2001;21:8168-83 pubmed..Our results define Man activation leading to GDP-Man as a virulence pathway in Leishmania. ..
- Ilgoutz S, Zawadzki J, Ralton J, McConville M. Evidence that free GPI glycolipids are essential for growth of Leishmania mexicana. EMBO J. 1999;18:2746-55 pubmed
- Sharma C, D Souza C, Elbein A. Partial purification of a mannosyltransferase involved in the O-mannosylation of glycoproteins from Saccharomyces cerevisiae. Glycobiology. 1991;1:367-73 pubmed..In general, mannosyltransferase was found to exhibit greater specificity for the L-alpha-PC derivatives in which the sn-2 position of the glycerol contained a saturated fatty acid.(ABSTRACT TRUNCATED AT 250 WORDS) ..
- Rush J, Waechter C. Expression of dolichol-linked saccharide intermediate synthesis during the development of B lymphocytes. Glycobiology. 1991;1:229-35 pubmed..abstract truncated at 250 words) ..
- Ware F, Lehrman M. Expression cloning of a novel suppressor of the Lec15 and Lec35 glycosylation mutations of Chinese hamster ovary cells. J Biol Chem. 1996;271:13935-8 pubmed..9 protein encoded on Caenorhabditis elegans chromosome 5. These results indicate a novel function for the SL15 protein and suggest that MPD synthesis is more complex than previously suspected...
- Szkopinska A, Rytka J, Karst F, Palamarczyk G. The deficiency of sterol biosynthesis in Saccharomyces cerevisiae affects the synthesis of glycosyl derivatives of dolichyl phosphates. FEMS Microbiol Lett. 1993;112:325-8 pubmed..It is postulated that the de novo synthesis of DolP is impaired in the ergosterol mutants. Moreover, a block in the ergosterol branch of the metabolic pathway (erg 9) causes an increase in the de novo synthesis of dolichyl phosphate...
- Ashida H, Maeda Y, Kinoshita T. DPM1, the catalytic subunit of dolichol-phosphate mannose synthase, is tethered to and stabilized on the endoplasmic reticulum membrane by DPM3. J Biol Chem. 2006;281:896-904 pubmed..Free DPM1 was strongly associated with the C terminus of Hsc70-interacting protein (CHIP), a chaperone-dependent E3 ubiquitin ligase, suggesting that DPM1 is ubiquitinated, at least in part, by CHIP. ..
- Maeda Y, Kinoshita T. Dolichol-phosphate mannose synthase: structure, function and regulation. Biochim Biophys Acta. 2008;1780:861-8 pubmed publisher..In this review, we focus on the biosynthesis of dolichol-phosphate-mannose, and particularly on the mammalian enzyme complex involved in the reaction. ..
- Freeze H, Willies L, Hamilton S, Koza Taylor P. Two mutants of Dictyostelium discoideum that lack a sulfated carbohydrate antigenic determinant synthesize a truncated lipid-linked precursor of N-linked oligosaccharides. J Biol Chem. 1989;264:5653-9 pubmed..These data along with the analysis of another mutant strain suggest that the expression of the antigenic determinant requires a specific arrangement of Man-6-SO4 on the alpha-1,6 branch of the oligosaccharide linked to the beta-mannose. ..
- Sanyal S, Menon A. Stereoselective transbilayer translocation of mannosyl phosphoryl dolichol by an endoplasmic reticulum flippase. Proc Natl Acad Sci U S A. 2010;107:11289-94 pubmed publisher..These data provide a mechanistic framework for understanding MPD flipping, as well as a biochemical basis for identifying MPD flippase. ..
- Duvet S, Chirat F, Mir A, Verbert A, Dubuisson J, Cacan R. Reciprocal relationship between alpha1,2 mannosidase processing and reglucosylation in the rough endoplasmic reticulum of Man-P-Dol deficient cells. Eur J Biochem. 2000;267:1146-52 pubmed..Thus, the trimming of Man5GlcNAc2 to Man4GlcNAc2, which is catalyzed by this mannosidase, could be involved in the control of the glucose-dependent folding pathway. ..
- Baulard A, Gurcha S, Engohang Ndong J, Gouffi K, Locht C, Besra G. In vivo interaction between the polyprenol phosphate mannose synthase Ppm1 and the integral membrane protein Ppm2 from Mycobacterium smegmatis revealed by a bacterial two-hybrid system. J Biol Chem. 2003;278:2242-8 pubmed..This interaction is reminiscent of that of mammalian Dpm1 with Dpm3 and mimics the structure of MtPpm1 as demonstrated by the capacity of the two domains of MtPpm1 to spontaneously interact when co-expressed in E. coli. ..
- Armstrong C, Schubert J, Ueda E, Knez J, Gelperin D, Hirose S, et al. Affected paroxysmal nocturnal hemoglobinuria T lymphocytes harbor a common defect in assembly of N-acetyl-D-glucosamine inositol phospholipid corresponding to that in class A Thy-1- murine lymphoma mutants. J Biol Chem. 1992;267:25347-51 pubmed
- Smith D, Proudfoot A, Friedli L, Klig L, Paravicini G, Payton M. PMI40, an intron-containing gene required for early steps in yeast mannosylation. Mol Cell Biol. 1992;12:2924-30 pubmed..PMI enzyme activity, however, is not increased in D-mannose-grown cells, and PMI protein levels remain constant, suggesting that the PMI40 gene is subject to additional levels of regulation. ..
- Azzouz N, Gerold P, Kedees M, Shams Eldin H, Werner R, Capdeville Y, et al. Regulation of Paramecium primaurelia glycosylphosphatidyl-inositol biosynthesis via dolichol phosphate mannose synthesis. Biochimie. 2001;83:801-9 pubmed..Furthermore, our data suggest that GTP gamma S interferes with synthesis of dolichol monophosphate, indicating that the dolichol kinase is regulated by the heterotrimeric G proteins. ..
- Anand M, Rush J, Ray S, Doucey M, Weik J, Ware F, et al. Requirement of the Lec35 gene for all known classes of monosaccharide-P-dolichol-dependent glycosyltransferase reactions in mammals. Mol Biol Cell. 2001;12:487-501 pubmed publisher..The in vitro data suggest that Lec35p controls an aspect of MPD orientation in the endoplasmic reticulum membrane that is crucial for its activity as a donor substrate...
- Karson E, Ballou C. Biosynthesis of yeast mannan. Properties of a mannosylphosphate transferase in Saccharomyces cerevisiae. J Biol Chem. 1978;253:6484-92 pubmed..A new mannan mutant class with the mnn4 chemotype was isolated, but the mutation proved to be recessive and nonallelic with the mnn4 locus. This new locus is designated mnn6. ..
- Maeda Y, Tomita S, Watanabe R, Ohishi K, Kinoshita T. DPM2 regulates biosynthesis of dolichol phosphate-mannose in mammalian cells: correct subcellular localization and stabilization of DPM1, and binding of dolichol phosphate. EMBO J. 1998;17:4920-9 pubmed..Mammalian DPM1 is catalytic because a fusion protein of DPM1 that was stably expressed in the ER synthesized DPM without DPM2. Therefore, biosynthesis of DPM in mammalian cells is regulated by DPM2. ..
- Villagómez Castro J, Calvo Méndez C, Vargas Rodríguez L, Flores Carreón A, Lopez Romero E. Entamoeba histolytica: solubilization and biochemical characterization of dolichol phosphate mannose synthase, an essential enzyme in glycoprotein biosynthesis. Exp Parasitol. 1998;88:111-20 pubmed..Mg2+ was a better activator of the reverse reaction than Mn2+, which reached up to 60% at 2 mM GDP. These results suggest that some of the enzyme catalytic properties may change depending on the direction of the transfer reaction. ..
- deGasperi R, Thomas L, Sugiyama E, Chang H, Beck P, Orlean P, et al. Correction of a defect in mammalian GPI anchor biosynthesis by a transfected yeast gene. Science. 1990;250:988-91 pubmed
- McDowell W, Grier T, Rasmussen J, Schwarz R. The role of C-4-substituted mannose analogues in protein glycosylation. Effect of the guanosine diphosphate esters of 4-deoxy-4-fluoro-D-mannose and 4-deoxy-D-mannose on lipid-linked oligosaccharide assembly. Biochem J. 1987;248:523-31 pubmed..Nearly normal extents of protein glycosylation were observed, but very little processing to complex oligosaccharides occurred, and the high-mannose structures were smaller than in untreated cells. ..
- Kean E, Rush J, Waechter C. Activation of GlcNAc-P-P-dolichol synthesis by mannosylphosphoryldolichol is stereospecific and requires a saturated alpha-isoprene unit. Biochemistry. 1994;33:10508-12 pubmed
- Dotson S, Rush J, Ricketts A, Waechter C. Mannosylphosphoryldolichol-mediated O-mannosylation of yeast glycoproteins: stereospecificity and recognition of the alpha-isoprene unit by a purified mannosyltransferase. Arch Biochem Biophys. 1995;316:773-9 pubmed
- Watanabe R, Murakami Y, Marmor M, Inoue N, Maeda Y, Hino J, et al. Initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-P and is regulated by DPM2. EMBO J. 2000;19:4402-11 pubmed..These results reveal new essential and regulatory components of GPI-GnT and imply co-regulation of GPI-GnT and the dolichol-phosphate-mannose synthase that generates a mannosyl donor for GPI. ..
- Sharma C, Radhakrishnamurthy B, Berenson G. Activation of dolichol-phosphate mannosyltransferase by dibutryl cyclic AMP in rat liver. Biochem Biophys Res Commun. 1988;155:615-21 pubmed..The activation of this enzyme could be through phosphorylation/dephosphorylation mechanism involving a cAMP dependent protein kinase. ..
- Sharma C, Dalferes E, Radhakrishnamurthy B, Depaolo C, Berenson G. Hepatic glycoprotein synthesis in streptozotocin diabetic rats. Biochem Int. 1987;15:395-401 pubmed..These results indicate that key intermediates in glycoprotein biosynthesis are regulated by insulin. ..
- Ruiz Baca E, Villagomez Castro J, Leal Morales C, Sabanero Lopez M, Flores Carreón A, Lopez Romero E. Biosynthesis of glycoproteins in the human pathogenic fungus Sporothrix schenckii: synthesis of dolichol phosphate mannose and mannoproteins by membrane-bound and solubilized mannosyl transferases. Antonie Van Leeuwenhoek. 2005;88:221-30 pubmed..The experimental approach described here can be used to identify and isolate specific glycoproteins mannosylated in vitro in studies of O-glycosylation. ..
- Horst M. Isolation of a crustacean N-acetyl-D-glucosamine-1-phosphate transferase and its activation by phospholipids. J Comp Physiol B. 1990;159:777-88 pubmed..Following hydrophobic interaction chromatography on Phenyl Sepharose, gel filtration chromatography on Sepharose CL-4B indicated that the enzyme, purified 81-fold, contained phophatidylcholine and phosphatidyl-ethanolamine. ..
- Pan Y, Elbein A. Control of N-linked oligosaccharide synthesis: cellular levels of dolichyl phosphate are not the only regulatory factor. Biochemistry. 1990;29:8077-84 pubmed
- Schutzbach J, Zimmerman J. Yeast dolichyl-phosphomannose synthase: reconstitution of enzyme activity with phospholipids. Biochem Cell Biol. 1992;70:460-5 pubmed
- Banerjee D. Amphomycin inhibits mannosylphosphoryldolichol synthesis by forming a complex with dolichylmonophosphate. J Biol Chem. 1989;264:2024-8 pubmed..These data demonstrated that amphomycin interacted with the active site of the glycosyl-carrier lipid (Dol-P), thereby preventing its participation at the enzymatic reaction. ..
- Grabińska K, Ghosh S, Guan Z, Cui J, Raetz C, Robbins P, et al. Dolichyl-phosphate-glucose is used to make O-glycans on glycoproteins of Trichomonas vaginalis. Eukaryot Cell. 2008;7:1344-51 pubmed publisher..To our knowledge, this is the first demonstration of Dol-P-Glc as a sugar donor for O-glycans on glycoproteins. ..
- Chapman A, Calhoun J. Effects of glucose starvation and puromycin treatment on lipid-linked oligosaccharide precursors and biosynthetic enzymes in Chinese hamster ovary cells in vivo and in vitro. Arch Biochem Biophys. 1988;260:320-33 pubmed
- Lamani E, Mewbourne R, Fletcher D, Maltsev S, Danilov L, Veselovsky V, et al. Structural studies and mechanism of Saccharomyces cerevisiae dolichyl-phosphate-mannose synthase: insights into the initial step of synthesis of dolichyl-phosphate-linked oligosaccharide chains in membranes of endoplasmic reticulum. Glycobiology. 2006;16:666-78 pubmed..The data allowed for proposing a molecular mechanism of catalysis as an inverting mechanism of mannosyl residue transfer. ..
- Strahl Bolsinger S, Tanner W. Protein O-glycosylation in Saccharomyces cerevisiae. Purification and characterization of the dolichyl-phosphate-D-mannose-protein O-D-mannosyltransferase. Eur J Biochem. 1991;196:185-90 pubmed..Thus acidic amino acids strongly inhibit acceptor activity as do glycine and proline residues as amino-terminal and carboxy-terminal neighbours, respectively. ..
- Frank C, Aebi M. ALG9 mannosyltransferase is involved in two different steps of lipid-linked oligosaccharide biosynthesis. Glycobiology. 2005;15:1156-63 pubmed..This report completes the list of lumen-oriented glycosyltransferases required for the assembly of the LLO. ..
- Moody D, Ulrichs T, Muhlecker W, Young D, Gurcha S, Grant E, et al. CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature. 2000;404:884-8 pubmed
- Oriol R, Martinez Duncker I, Chantret I, Mollicone R, Codogno P. Common origin and evolution of glycosyltransferases using Dol-P-monosaccharides as donor substrate. Mol Biol Evol. 2002;19:1451-63 pubmed
- Singh N, Tartakoff A. Two different mutants blocked in synthesis of dolichol-phosphoryl-mannose do not add glycophospholipid anchors to membrane proteins: quantitative correction of the phenotype of a CHO cell mutant with tunicamycin. Mol Cell Biol. 1991;11:391-400 pubmed..Thus, two mutations can interrupt DPM synthesis, and three sets of observations point to an essential role of DPM for addition of GPL anchors. ..
- Hong Y, Maeda Y, Watanabe R, Inoue N, Ohishi K, Kinoshita T. Requirement of PIG-F and PIG-O for transferring phosphoethanolamine to the third mannose in glycosylphosphatidylinositol. J Biol Chem. 2000;275:20911-9 pubmed..Therefore, mammalian cells have redundant activities in transferring phosphoethanolamine to the third mannose, both of which require PIG-F. ..