Skip to main content
SpringerLink
Log in

The joys of HexNAc. The synthesis and function of N-andO-glycan branches

  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

This review covers discoveries made over the past 30–35 years that were important to our understanding of the synthetic pathway required for initiation of the antennae or branches on complex N-glycans and O-glycans. The review deals primarily with the author's contributions but the relevant work of other laboratories is also discussed. The focus of the review is almost entirely on the glycosyltransferases involved in the process. The following topics are discussed. (1) The localization of the synthesis of complex N-glycan antennae to the Golgi apparatus. (2) The “evolutionary boundary” at the stage in N-glycan processing where there is a change from oligomannose to complex N-glycans; this switch correlates with the appearance of multicellular organisms. (3) The discovery of the three enzymes which play a key role in this switch, N-acetylglucosaminyltransferases I and II and mannosidase II. (4) The “yellow brick road” which leads from oligomannose to highly branched complex N-glycans with emphasis on the enzymes involved in the process and the factors which control the routes of synthesis. (5) A short discussion of the characteristics of the enzymes involved and of the genes that encode them. (6) The role of complex N-glycans in mammalian and Caenorhabditis elegans development. (7) The crystal structure of N-acetylglucosaminyltransferase I. (8) The discovery of the enzymes which synthesize O-glycan cores 1, 2, 3 and 4 and their elongation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Schachter H, The “yellow brick road” to branched complex N-glycans, Glycobiology 1, 453–61 (1991).

    Google Scholar 

  2. Smithies O, Connell GE, Dixon GH, Gene action in the human haptoglobins. I. Dissociation into constituent polypeptide chains, Journal of Molecular Biology 21, 213–24 (1966).

    Google Scholar 

  3. Connell GE, Smithies O, Dixon GH, Gene action in the human haptoglobins. II. Isolation and physical characterization of alpha polypeptide chains, Journal of Molecular Biology 21, 225–9 (1966).

    Google Scholar 

  4. Schachter H, Dixon GH, Preferential oxidation of the methionine residue near the active site of chymotrypsin, J Biol Chem 239, 813–29 (1964).

    Google Scholar 

  5. Roseman S, Distler JJ, Moffat JG, Khorana HG, Nucleoside polyphosphates. XI. An Improved general method for the synthesis of nucleoside coenzymes. Syntheses of uridine-5', cytidine-5' and guanosine-5' diphosphat derivatives, J Am Chem Soc 83, 659–63 (1961).

    Google Scholar 

  6. Schachter H, Ishihara H, Heath EC, GDP-L-(14C) Fucose. In Methods in Enzymology. Complex Carbohydrates, edited by Ginsburg V, Part B. Vol. 28 (Academic Press, New York, NY, 1972), pp. 285–7.

    Google Scholar 

  7. Schachter H, Sarney J, McGuire EJ, Roseman S, Isolation of diphosphopyridine nucleotide-dependent L-fucose dehydrogenase from pork liver, J Biol Chem 244, 4785–92 (1969).

    Google Scholar 

  8. Finch P, Yuen R, Schachter H, Moscarello M, Enzymic methods for the micro-assay of D-mannose, D-glucose, D-galactose and L-fucose from acid hydrolysates of glycoproteins, Anal Biochem 31, 296–305 (1969).

    Google Scholar 

  9. Nwokoro NA, Schachter H, L-fucose metabolism in mammals. II: Purification of pork liver 2-keto-3-deoxy-L-fuconate: NAD+. oxidoreductase by NAD+.-agarose affinity chromatography, J Biol Chem 250, 6185–90 (1975).

    Google Scholar 

  10. Nwokoro NA, Schachter H, L-fucose metabolism in mammals. III: Kinetic studies on pork liver 2-keto-3-deoxy-L-fuconate: NAD+. oxidoreductase, J Biol Chem 250, 6191–6 (1975).

    Google Scholar 

  11. Chan JY, Nwokoro N, Schachter H, L-Fucose metabolism in Mammals. IV. The conversion of L-Fucose to two moles of L-lactate, of L-galactose to L-lactate and glycerate, and of D-arabinose to L-lactate and glycollate, J Biol Chem, 254, 7060–8 (1979).

    Google Scholar 

  12. Yuen R, Schachter H, L-fucose metabolism in mammals. I: Pork liver L-fuconate hydro-lyase, Can J Biochem 50, 798–806 (1972).

    Google Scholar 

  13. Schachter H, Jabbal I, Hudgin RL, Pinteric L, McGuire EJ, Roseman S, Intracellular localization of nucleotide sugar: glycoprotein glycosyltransferases in a Golgi-rich fraction, J Biol Chem 245, 1090–100 (1970).

    Google Scholar 

  14. Schachter H, Rodén L, The biosynthesis of animal glycoproteins. In Metabolic Conjugation and Metabolic Hydrolysis, edited by Fishman WH, Vol. III (Academic Press, New York, NY, 1973), pp. 1–149.

    Google Scholar 

  15. Morré DJ, Hamilton RL, Mollenhauer HH, Mahley RW, Cunningham WP, Cheetham RD, Lequire VS, Isolation of a Golgi apparatus-rich fraction from rat liver. I. Method and morphology, Journal of Cell Biology 44, 484–91 (1970).

    Google Scholar 

  16. Yunghans WN, Keenan TW, Morré DJ, Isolation of golgi apparatus from rat liver. 3. Lipid and protein composition, Experimental & Molecular Pathology 12, 36–45 (1970).

    Google Scholar 

  17. Morré DJ, Cheetham RD, Nyquist SE, A simplified procedure for isolation of golgi apparatus from rat liver, Preparative Biochemistry 2, 61–9 (1972).

    Google Scholar 

  18. Merritt WD, Morré DJ, A glycosyl transferase of high specific activity in secretory vesicles from isolated Golgi apparatus of rat liver, Biochimica et Biophysica Acta 304, 397–407 (1973).

    Google Scholar 

  19. Munro JR, Narasimhan S, Wetmore S, Riordan JR, Schachter H, Intracelular localization of GDP-L-fucose: glycoprotein and CMP-sialic acid: apolipoprotein glycosyltransverases in rat and pork liver, Arch Biochem Biophys 169, 269–77 (1975).

    Google Scholar 

  20. Fleischer B, Mechanism of glycosylation in the Golgi apparatus, Journal of Histochemistry & Cytochemistry 31, 1033–40 (1983).

    Google Scholar 

  21. Kornfeld R, Kornfeld S, Assembly of asparagine-linked oligosaccharides, Ann Rev Biochem 54, 631–64 (1985).

    Google Scholar 

  22. Schachter H, Roseman S, Mammalian glycosyltransferases: their role in the synthesis and function of complex carbohydrates and glycolipids. In Biochemistry of Glycoproteins and Proteoglycans, edited by Lennarz WJ, (Plenum Press, New York, NY, 1980), pp. 85–160.

    Google Scholar 

  23. Dorland L, Schut BL, Vliegenthart JFG, Strecker G, Fournet B, Spik G, Montreuil J, Structural studies on 2-acetamido-1-N-(4-L-aspartyl)-2-deoxy-beta-D-glucopyranosylamine and 2-acetamido-6-O-(alpha-L-fucopyranosyl)-1-N-(4-L-aspartyl)-2-deoxy-beta-D-glucopyranosylamine by 360-MHz proton magnetic resonance spectroscopy, Eur J Biochem 73, 93–7 (1977).

    Google Scholar 

  24. Dorland L, Haverkamp J, Schut BL, Vliegenthart JFG, Spik G, Strecker G, Fournet B, Montreuil J, The structure of the asialocarbohydrate units of human serotransferrin as proven by 360MHz proton magnetic resonance spectroscopy, FEBS Lett 77, 15–20 (1977).

    Google Scholar 

  25. Dorland L, Haverkamp J, Vliegenthart JFG, Strecker G, Michaiski J-C, Fournet B, Spik G, Montreuil J, 360-MHz proton nuclear magnetic resonance spectroscopy of sialyl oligosaccharides from patients with sialidosis (mucolipidosis I and II), Eur J Biochem 87, 323–9 (1978).

    Google Scholar 

  26. Leger D, Tordera V, Spik G, Dorland L, Haverkamp J, Vliegenthart JFG, Structure determination of the single glycan of rabbit serotransferrin by methylation analysis and 360MHz proton nuclear magnetic resonance spectroscopy, FEBS Lett 93, 255–60 (1978).

    Google Scholar 

  27. van Halbeek H, Dorland L, Vliegenthart JFG, Fiat AM, Jolles P, A 360-MHz 1H-NMR study of three oligosaccharides isolated from cow kappa-casein, Biochim Biophys Acta 623, 295–300 (1980).

    Google Scholar 

  28. van Halbeek H, Dorland L, Haverkamp J, Veldink GA, Vliegenthart JFG, Fournet B, Ricart G, Montreuil J, Gathmann WD, Aminoff D, Structure determination of oligosaccharides isolated from A.+, H.+ and A-H-hog-submaxillary-gland mucin glycoproteins, by 360-MHz 1H-NMR spectroscopy, permethylation analysis and mass spectrometry, Eur J Biochem 118, 487–95 (1981).

    Google Scholar 

  29. Barker R, Olsen KW, Shaper JH, Hill RL, Agarose derivatives of uridine diphosphate and N-acetylglucosamine for the purification of a galactosyltransferase, J Biol Chem 247, 7135–47 (1972).

    Google Scholar 

  30. Beyer TA, Rearick JI, Paulson JC, Prieels JP, Sadler JE, Hill RL, Biosynthesis of mammalian glycoproteins. Glycosylation pathways in the synthesis of the non-reducing terminal sequences, J Biol Chem 254, 12531–41 (1979).

    Google Scholar 

  31. Beyer TA, Sadler JE, Rearick JI, Paulson JC, Hill RL, Glycosyltransferases and their use in assessing oligosaccharide structure and structure-function relationships. In Advances in Enzymology, edited by Meister A, Vol. 52 (John Wiley and Sons, New York, 1981), pp. 23–175.

    Google Scholar 

  32. Hunt LA, Etchison JR, Summers DF, Oligosaccharide chains are trimmed during synthesis of the envelope glycoprotein of vesicular stomatitis virus, Proc Natl Acad Sci USA 75, 754–8 (1978).

    Google Scholar 

  33. Kornfeld R, Kornfeld S, Structure of glycoproteins and their oligosaccharide units. In The Biochemistry of Glycoproteins and Proteoglycans, edited by Lennarz WJ, (Plenum Press, New York, NY, 1980), pp. 1–34.

    Google Scholar 

  34. Robbins PW, Hubbard SC, Turco SJ, Wirth DF, Proposal for a common oligosaccharide intermediate in the synthesis of membrane glycoproteins, Cell 12, 893–900 (1977).

    Google Scholar 

  35. Tabas I, Schlesinger S, Kornfeld S, The processing of high mannose oligosaccharides to form complex type oligosaccharides in the newly synthesized polypeptides of the vesicular stomatitis virus G protein and the IgG heavy chain, J Biol Chem 253, 716–22 (1978).

    Google Scholar 

  36. Hubbard SC, Robbins PW, Synthesis and processing of proteinlinked oligosaccharides in vivo, J Biol Chem 254, 4568–76 (1979).

    Google Scholar 

  37. Johnston IR, McGuire EJ, Jourdian GW, Roseman S, Incorporation of N-acetyl-D-glucosamine into glycoproteins, J Biol Chem 241, 5735–7 (1966).

    Google Scholar 

  38. Dennis JW, Carver JP, Schachter H, Asparagine-linked oligosaccharides in murine tumor cells: comparison of a WGA-resistant non-metastatic mutant and a related WGA-sensitive metastatic line, J Cell Biol 99, 1034–44 (1984).

    Google Scholar 

  39. Narasimhan S, Harpaz N, Longmore G, Carver JP, Grey AA, Schachter H, Control of glycoprotein synthesis. The purification by preparative high voltage electrophoresis in borate of glycopeptides containing high mannose and complex oligosaccharide chains linked to asparagine, J Biol Chem 255, 4876–84 (1980).

    Google Scholar 

  40. Grey AA, Narasimhan S, Brisson JR, Schachter H, Carver JP, Structure of the glycopeptides of a human gamma 1-immunoglobulin G (Tem) myeloma protein as determined by 360-megahertz nuclear magnetic resonance spectroscopy, Canadian Journal of Biochemistry 60, 1123–31 (1982).

    Google Scholar 

  41. Narasimhan S, Stanley P, Schachter H, Control of glycoprotein synthesis. II. Lectin-resistant mutant containing only one of two distinct N-acetylglucosaminyltransferase activities present in wild type Chinese hamster ovary cells, J Biol Chem 252, 3926–33 (1977).

    Google Scholar 

  42. Stanley P, Narasimhan S, Siminovitch L, Schachter H, Chinese hamster ovary cells selected for resistance to the cytotoxicity of phytohemagglutinin are deficient in a UDP-N-acetylglucosamine: glycoprotein N-acetylglucosaminyltransferase activity, Proc Nat Acad Sci (USA) 72, 3323–7 (1975).

    Google Scholar 

  43. Robertson MA, Etchison JR, Robertson JS, Summers DF, Stanley P, Specific changes in the oligosaccharide moieties of VSV grown in different lectin-resistant CHO cells, Cell 13, 515–26 (1978).

    Google Scholar 

  44. Schlesinger S, Gottlieb C, Feil P, Gelb N, Kornfeld S, Growth of enveloped RNA viruses in a line of chinese hamster ovary cells with deficient N-acetylglucosaminyltransferase activity, Journal of Virology 17, 239–46 (1975).

    Google Scholar 

  45. Gottlieb C, Baenziger J, Kornfeld S, Deficient uridine diphosphate-N-acetylglucosamine: glycoprotein N-acetylglucosaminyltransferase activity in a clone of Chinese hamster ovary cells with altered surface glycoproteins, J Biol Chem 250, 3303–9 (1975).

    Google Scholar 

  46. Vischer P, Hughes RC, Glycosyl transferases of baby-hamsterkidney (BHK) cells and ricin-resistant mutants. N-glycan biosynthesis, Eur J Biochem 117, 275–84 (1981).

    Google Scholar 

  47. Li E, Kornfeld S, Structure of the altered oligosaccharide present in glycoproteins from a clone of Chinese hamster ovary cells deficient in N-acetylglucosaminyltransferase activity, J Biol Chem 253, 6426–31 (1978).

    Google Scholar 

  48. Tabas I, Kornfeld S, The synthesis of complex-type oligosaccharides III. Identification of an ?-D-mannosidase activity involved in a late stage of processing of complex-type oligosaccharides, J Biol Chem 253, 7779–86 (1978).

    Google Scholar 

  49. Harpaz N, Schachter H, Control of glycoprotein synthesis. V. Processing of asparagine-linked oligosaccharides by one or more rat liver Golgi α-D-mannosidases dependent on the prior action of UDP-N-acetylglucosamine:α-?-mannoside ?-2-Nacetylglucosaminyltransferase I, J Biol Chem 255, 4894–902 (1980).

    Google Scholar 

  50. Kornfeld S, Gregory W, Chapman A, Class E Thy-1 negative mouse lymphoma cells utilize an alternate pathway of oligosaccharide processing to synthesize complex-type oligosaccharides, J Biol Chem 254, 11649–54 (1979).

    Google Scholar 

  51. Tulsiani DR, Opheim DJ, Touster O, Purification and characterization of alpha-D-mannosidase from rat liver golgi membranes, J Biol Chem 252, 3227–33 (1977).

    Google Scholar 

  52. Tulsiani DRP, Harris TM, Touster O, Swainsonine inhibits the biosynthesis of complex glycoproteins by inhibition of Golgi mannosidase II, J Biol Chem 257, 7936–9 (1982).

    Google Scholar 

  53. Tulsiani DR, Hubbard SC, Robbins PW, Touster O, alpha-D-Mannosidases of rat liver Golgi membranes. Mannosidase II is the GlcNAcMan5-cleaving enzyme in glycoprotein biosynthesis and mannosidases Ia and IB are the enzymes converting Man9 precursors to Man5 intermediates, J Biol Chem 257, 3660–8 (1982).

    Google Scholar 

  54. Moremen KW, Isolation of a rat liver Golgi mannosidase II clone by mixed oligonucleotide-primed amplification of cDNA, Proc Natl Acad Sci USA 86, 5276–80 (1989).

    Google Scholar 

  55. Moremen KW, Robbins PW, Isolation, characterization, and expression of cDNAs encoding murine alpha-mannosidase II, a Golgi enzyme that controls conversion of high mannose to complex N-glycans, J Cell Biol 115, 1521–34 (1991).

    Google Scholar 

  56. Misago M, Liao YF, Kudo S, Eto S, Mattei MG, Moremen KW, Fukuda MN, Molecular cloning and expression of cDNAs encoding human alpha-mannosidase II and a previously unrecognized alpha-mannosidase IIx isozyme, Proc Natl Acad Sci USA 92, 11766–70 (1995).

    Google Scholar 

  57. Schachter H, Biosynthetic controls that determine the branching and microheterogeneity of protein-bound oligosaccharides, Biochem Cell Biol 64, 163–81 (1986).

    Google Scholar 

  58. Schachter H, Narasimhan S, Gleeson P, Vella G, Control of branching during the biosynthesis of asparagine-linked oligosaccharides, Can J Biochem Cell Biol 61, 1049–66 (1983).

    Google Scholar 

  59. Schachter H, Narasimhan S, Gleeson P, Vella G, Brockhausen I, Glycosyltransferases involved in the biosynthesis of proteinbound oligosaccharides of the asparagine-N-acetyl-D-glucosamine and serine(threonine)-N-acetyl-D-galactosamine types. In The Enzymes of Biological Membranes Biosynthesis and Metabolism, edited by Martonosi AN, Vol. 2 (Plenum Press, New York, NY, 1985), pp. 227–77.

    Google Scholar 

  60. Staudacher E, Altmann F, Wilson IB, Marz L, Fucose in N-glycans: from plant to man, Biochim Biophys Acta 1473, 216–36 (1999).

    Google Scholar 

  61. Longmore GD, Schachter H, Control of Glycoprotein Synthesis. VI. Product identification and substrate specificity studies of the GDP-L-Fucose:2-acetamido-2-deoxy-α-D-glucoside (Fuc to Asn-linked GlcNAc) 6-β-L-fucosyltransferase in a Golgi-rich fraction form porcine liver, Carbohydrate Res 100, 365–92 (1982).

    Google Scholar 

  62. Johnson KD, Chrispeels MJ, Substrate specificities of N-acetylglucosaminyl-, fucosyl-, and xylosyltransferases that modify glycoproteins in the Golgi apparatus of bean cotyledons, Plant Physiol 84, 1301–8 (1987).

    Google Scholar 

  63. Mulder H, Dideberg F, Schachter H, Spronk BA, De Jong-Brink M, Kamerling JP, Vliegenthart JFG, In the biosynthesis of N-glycans in connective tissue of the snail Lymnaea stagnalis, incorporation of GlcNAc by beta-2-GlcNAc-transferase I is an essential prerequisite for the action of beta-2-GlcNAc-transferase II and beta-2-Xyl-transferase, Eur J Biochem 232, 272–83 (1995).

    Google Scholar 

  64. Staudacher E, Altmann F, Glössl J, März L, Schachter H, Kamerling JP, Hård K, Vliegenthart JFG, GDP-fucose: beta-N-acetylglucosamine (Fuc to (Fucalphal?6GlcNAc)-Asn-peptide) alphal?3-fucosyltransferase activity in honeybee (Apis mellifica) venom glands--The difucosylation of asparagine-bound N-acetylglucosamine, Eur J Biochem 199, 745–51 (1991).

    Google Scholar 

  65. Watkins WM, Biochemistry and genetics of the ABO, Lewis and P blood group systems. In Advances in Human Genetics, edited by Harris H, Hirschhorn K, Vol. 10 (Plenum Press, New York, NY, 1980), pp. 1–385.

    Google Scholar 

  66. Harpaz N, Schachter H, Control of glycoprotein synthesis. IV. Bovine colostrum UDP-N-acetylglucosamine: α-?-mannoside ?-2-N-acetylglucosaminyltransferase I. Separation from UDPN-acetylglucosamine: α-?-mannoside ?-2-N-acetylglucosaminyltransferase II, partial purification and substrate specificity, J Biol Chem 255, 4885–93 (1980).

    Google Scholar 

  67. Oppenheimer CL, Eckhardt AE, Hill RL, The non-identity of porcine N-acetylglucosaminyltransferases I and II, J Biol Chem 256, 11477–82 (1981).

    Google Scholar 

  68. Oppenheimer CL, Hill RL, Purification and characterization of a rabbit liver ?1-3 mannoside ?1-2 N-acetylglucosaminyltransferase, J Biol Chem 256, 799–804 (1981).

    Google Scholar 

  69. Nishikawa Y, Pegg W, Paulsen H, Schachter H, Control of glycoprotein synthesis. XV. Purification and characterization of rabbit liver UDP-N-acetylglucosamine: α-3-D-mannoside β-1,2-N-acetylglucosaminyltransferase I, J Biol Chem 263, 8270–81 (1988).

    Google Scholar 

  70. Bendiak B, Schachter H, Control of glycoprotein synthesis. XII. Purification of UDP-GlcNAc: α-?-mannoside ?1-2-N-acetylglucosaminyltransferase II from rat liver, J Biol Chem 262, 5775–83 (1987).

    Google Scholar 

  71. Allen SD, Tsai D, Schachter H, Control of glycoprotein synthesis. X. The in vitro synthesis by hen oviduct membrane preparations of hybrid asparagine-linked oligosaccharides containing 5 mannose residues, J Biol Chem 259, 6984–90 (1984).

    Google Scholar 

  72. Brockhausen I, Carver J, Schachter H, Control of Glycoprotein Synthesis. XIV. The use of oligosaccharide substrates and HPLC to study the sequential pathway for N-acetylglucosaminyltransferases I, II, III, IV, V and VI in the biosynthesis of highly branched N-glycans by hen oviduct membranes, Biochem Cell Biol 66, 1134–51 (1988).

    Google Scholar 

  73. Brockhausen I, Hull E, Hindsgaul O, Schachter H, Shah RN, Michnick SW, Carver JP, Control of glycoprotein synthesis. XVI. Detection and characterization of a novel branching enzyme from hen oviduct, UDP-N-acetylglucosamine: GlcNAc?1-6(GlcNAc?1-2)Man?-R (GlcNAc to Man) ?-4-N-acetylglucosaminyltransferase VI, J Biol Chem 264, 11211–21 (1989).

    Google Scholar 

  74. Gleeson PA, Schachter H, Control of Glycoprotein Synthesis. VIII. UDP-GlcNAc: GnGn (GlcNAc to Man?1-3) ?4-Nacetylglucosaminyltransferase IV, an enzyme in hen oviduct which adds GlcNAc in ?1-4 linkage to the ?1-3-linked Man residue of the trimannosyl core of N-glycosyl oligosaccharides to form a triantennary structure, J Biol Chem 258, 6162–73 (1983).

    Google Scholar 

  75. Narasimhan S, Control of Glycoprotein Synthesis. VII. UDPGlcNAc: glycopeptide ?4-N-acetylglucosaminyltransferase III, an enzyme in hen oviduct which adds GlcNAc in ?1-4 linkage to the ?-linked mannose of the trimannosyl core of N-glycosyl oligosaccharides, J Biol Chem 257, 10235–42 (1982).

    Google Scholar 

  76. Cummings RD, Trowbridge IS, Kornfeld S, A mouse lymphoma cell line resistant to the leukoagglutinating lectin from Phaseolus vulgaris is deficient in UDP-GlcNAc:α-?-mannoside ?1,6N-acetylglucosaminyltransferase, J Biol Chem 257, 13421–7 (1982).

    Google Scholar 

  77. Cummings RD, Kornfeld S, The distribution of repeating Gal?1-4GlcNAc?1-3 sequences in asparagine-linked oligosaccharides of the mouse lymphoma cell line BW5147 and PHAR2.1, J Biol Chem 259, 6253–60 (1984).

    Google Scholar 

  78. Nishikawa A, Ihara Y, Hatakeyama M, Kangawa K, Taniguchi N, Purification, cDNA cloning, and expression of UDP-N-acetylglucosamine: beta-D-mannoside beta-1,4N-acetylglucosaminyltransferase III from rat kidney, J Biol Chem 267, 18199–204 (1992).

    Google Scholar 

  79. Oguri S, Minowa MT, Ihara Y, Taniguchi N, Ikenaga H, Takeuchi M, Purification and characterization of UDP-N-acetylglucosamine: alpha 1,3-D-mannoside beta 1,4-N-acetylglucosaminyltransferase (N-acetylglucosaminyltransferase-IV) from bovine small intestine, J Biol Chem 272, 22721–7 (1997).

    Google Scholar 

  80. Shoreibah MG, Hindsgaul O, Pierce M, Purification and characterization of rat kidney UDP-N-acetylglucosamine: alpha-6-D-Mannoside beta-1,6-N-acetylglucosaminyltransferase, J Biol Chem 267, 2920–7 (1992).

    Google Scholar 

  81. Gu J, Nishikawa A, Tsuruoka N, Ohno M, Yamaguchi N, Kanagawa K, Taniguchi N, Purification and characterization of UDP-N-acetylglucosamine: alpha-6-D-mannoside beta1-6N-acetylglucosaminyltransferase (N-acetylglucosaminyltransferase V) from a human lung cancer cell line, J Biochem 113, 614–9 (1993).

    Google Scholar 

  82. Vella GJ, Paulsen H, Schachter H, Control of glycoprotein synthesis. IX. A terminal Man?1-3Man?1-sequence in the substrate is the minimum requirement for UDP-N-acetylglucosamine: α-?-mannoside (GlcNAc to Mana1-3-) ?2-N-acetylglucosaminyltransferase I, Can J Biochem Cell Biol 62, 409–17 (1984).

    Google Scholar 

  83. Brockhausen I, Möller G, Yang JM, Khan SH, Matta KL, Paulsen H, Grey AA, Shah RN, Schachter H, Control of glycoprotein synthesis. Characterization of (1?4)-N-acetylbeta-D-glucosaminyltransferases acting on the alpha-D-(1?3)-and alpha-D-(1?6)-linked arms of N-linked oligosaccharides, Carbohydr Res 236, 281–99 (1992).

    Google Scholar 

  84. Möller G, Reck F, Paulsen H, Kaur KJ, Sarkar M, Schachter H, Brockhausen I, Control of glycoprotein synthesis: Substrate specificity of rat liver UDP-GlcNAc: Manalpha3R beta2-N-acetylglucosaminyltransferase I using synthetic substrate analogues, Glycoconjugate J 9, 180–90 (1992).

    Google Scholar 

  85. Brockhausen I, Reck F, Kuhns W, Khan S, Matta KL, Meinjohanns E, Paulsen H, Shah RN, Baker MA, Schachter H, Substrate specificity and inhibition of UDP-GlcNAc: GlcNAc beta 1-2Man alpha 1-6R beta 1-6-N-acetylglucosaminyltransferase V using synthetic substrate analogues, Glycoconjugate J 12, 371–9 (1995).

    Google Scholar 

  86. Paulsen H, Reck F, Meinjohanns E, Springer M, Brockhausen I, Schachter H, Synthesis of partial structures of glycoproteins of substrates for glycosyltransferases. In Complex Carbohydrates in Drug Research, Alfred Benzon Symposium, edited by Bock K, Clausen H, Vol. 36 (Munksgaard, Copenhagen, 1994), pp. 78–86.

    Google Scholar 

  87. Reck F, Springer M, Paulsen H, Brockhausen I, Sarkar M, Schachter H, Synthesis of tetrasaccharide analogues of the Nglycan substrate of beta-(1?2)-N-acetylglucosaminyltransferase II using trisaccharide precursors and recombinant beta( 1?2)-N-acetylglucosaminyltransferase I, Carbohydr Res 259, 93–101 (1994).

    Google Scholar 

  88. Reck F, Meinjohanns E, Springer M, Wilkens R, Van Dorst JALM, Paulsen H, Moller G, Brockhausen I, Schachter H, Synthetic substrate analogues for UDP-GlcNAc: Man alpha 1-6R beta(1-2)-n-acetylglucosaminyltransferase II. Substrate specificity and inhibitors for the enzyme [published erratum appears in Glycoconj J 1994 Dec;11(6):i], Glycoconjugate J 11, 210–16 (1994).

    Google Scholar 

  89. Paulsen H, Springer M, Reck F, Meinjohanns E, Brockhausen I, Schachter H, Building units of oligosaccharides. 109. Synthesis of modified oligosaccharides of N-glycoproteins for substrate specificity studies of N-acetylglucosaminyltransferase I, Liebigs Annalen 53–66 (1995).

  90. Paulsen H, Springer M, Reck F, Brockhausen I, Schachter H, Building units of oligosaccharides. 110. Synthesis of potential inhibitors of N-acetylglucosaminyltransferase I, Liebigs Annalen 67–76 (1995).

  91. Paulsen H, Springer M, Reck F, Brockhausen I, Schachter H, Synthesis of modified tetrasaccharides as acceptor-inhibitor analogs of N-acetylglucosaminyltransferase II, Carbohydr Res 275, 403–11 (1995).

    Google Scholar 

  92. Reck F, Meinjohanns E, Tan J, Grey AA, Paulsen H, Schachter H, Synthesis of pentasaccharide analogues of the N-glycan substrates of N-acetylglucosaminyltransferases III, IV and V using tetrasaccharide precursors and recombinant beta-(1?2)-Nacetylglucosaminyltransferase II, Carbohydr Res 275, 221–9 (1995).

    Google Scholar 

  93. Reck F, Springer M, Meinjohanns E, Paulsen H, Brockhausen I, Schachter H, Synthetic substrate analogues for UDP-GlcNAc: Man alpha 1-3R beta 1-2-N-acetylglucosaminyltransferase I. Substrate specificity and inhibitors for the enzyme, Glycoconjugate J 12, 747–54 (1995).

    Google Scholar 

  94. Palcic MM, Heerze LD, Pierce M, Hindsgaul O, The use of hydrophobic synthetic glycosides as acceptors in glycosyltransferase assays, Glycoconjugate J 5, 49–63 (1988).

    Google Scholar 

  95. Bendiak B, Schachter H, Control of glycoprotein synthesis. XIII. Kinetic mechanism, substrate specificity, and inhibition characteristics of UDP-GlcNAc: α-?-mannoside ?1-2-N-acety1glucosaminyltransferase II from rat liver, J Biol Chem 262, 5784–90 (1987).

    Google Scholar 

  96. Mulder H, Schachter H, De Jong-Brink M, Van Der Ven JGM, Kamerling JP, Vliegenthart JFG, Identification of a novel UDPGal: GalNAcbeta1-4GlcNAc-R beta1-3-galactosyltransferase in the connective tissue of the snail Lymnaea stagnalis, Eur J Biochem 201, 459–65 (1991).

    Google Scholar 

  97. Mulder H, Spronk BA, Schachter H, Neeleman AP, Van den Eijnden DH, De Jong-Brink M, Kamerling JP, Vliegenthart JFG, Identification of a novel UDP-GalNAc: GlcNAc beta-R beta1-4 N-acetylgalactosaminyltransferase from the albumen gland and connective tissue of the snail Lymnaea stagnalis. Eur J Biochem 227, 175–85 (1995).

    Google Scholar 

  98. Mulder H, Schachter H, Thomas JR, Halkes KM, Kamerling JP, Vliegenthart FG, Identification of a GDP-Fuc: Gal beta 1-3GalNAc-R (Fuc to Gal) alpha 1-2 fucosyltransferase and a GDP-Fuc: Gal beta1-4GlcNAc (Fuc to GlcNAc) alpha 1-3 fucosyltransferase in connective tissue of the snail Lymnaea stagnalis, Glycoconjugate J 13, 107–13 (1996).

    Google Scholar 

  99. Sarkar M, Hull E, Simpson RJ, Moritz RL, Dunn R, Schachter H, Rabbit liver UDP-N-Acetylglucosamine: α-3-D-mannoside β-1,2-N-acetylglucosaminyltransferase I: characterization of a 2.5 kilobase cDNA clone, Glycoconjugate J 7, 380 (1990).

    Google Scholar 

  100. Sarkar M, Hull E, Nishikawa Y, Simpson RJ, Moritz RL, Dunn R, Schachter H, Molecular cloning and expression of cDNA encoding the enzyme that controls conversion of high-mannose to hybrid and complex N-glycans: UDP-N-acetylglucosamine: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I, Proc Natl Acad Sci USA 88, 234–8 (1991).

    Google Scholar 

  101. Hull E, Schachter H, Sarkar M, Spruijt MPN, Höppener JWM, Roovers D, Dunn R, Isolation of 13 and 15 kilobase human genomic DNA clones containing the gene for UDP-N-Acetylglucosamine: α-3-D-mannoside β-1,2-N-acetylglucosaminyltransferase I, Glycoconjugate J 7, 468 (1990).

    Google Scholar 

  102. Hull E, Sarkar M, Spruijt MPN, Höppener JWM, Dunn R, Schachter H, Organization and localization to chromosome 5 of the human UDP-N-acetylglucosamine: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I gene, Biochem Biophys Res Commun 176, 608–15 (1991).

    Google Scholar 

  103. Kumar R, Yang J, Larsen RD, Stanley P, Cloning and expression of N-acetylglucosaminyltransferase I, the medial Golgi transferase that initiates complex N-linked carbohydrate formation, Proc Natl Acad Sci USA 87, 9948–52 (1990).

    Google Scholar 

  104. D'Agostaro GAF, Zingoni A, Simpson RJ, Moritz RL, Schachter H, Bendiak BK, Molecular cloning and expression of cDNA encoding rat UDP-N-acetylglucosamine:?-6-D-mannoside ?-1,2-N-acetylglucosaminyltransferase II, Glycoconjugate J 10, 234 (1993).

    Google Scholar 

  105. D'Agostaro GAF, Zingoni A, Moritz RL, Simpson RJ, Schachter H, Bendiak B, Molecular cloning and expression of cDNA encoding the rat UDP-N-acetylglucosamine: alpha-6-Dmannoside beta-1,2-N-acetylglucosaminyltransferase II, J Biol Chem 270, 15211–21 (1995).

    Google Scholar 

  106. Tan J, D'Agostaro GAF, Bendiak BK, Squire J, Schachter H, Molecular cloning and localization to chromosome 14 of the human UDP-N-acetylglucosamine: ?-6-D-mannoside ?-1,2-Nacetylglucosaminyltransferase II gene (MGAT2), Glycoconjugate J 10, 232–3 (1993).

    Google Scholar 

  107. Tan J, D'Agostaro GAF, Bendiak B, Reck F, Sarkar M, Squire JA, Leong P, Schachter H, The human UDP-Nacetylglucosamine: alpha-6-D-mannoside-beta-1,2-N-acetylglucosaminyltransferase II gene (MGAT2)--Cloning of genomic DNA, localization to chromosome 14q21, expression in insect cells and purification of the recombinant protein, Eur J Biochem 231, 317–28 (1995).

    Google Scholar 

  108. Chen SH, Zhou SH, Tan J, Schachter H, Transcriptional regulation of the human UDP-GlcNAc: alpha-6-D-mannoside beta-1-2-N-acetylglucosaminyltransferase II gene (MGAT2) which controls complex N-glycan synthesis, Glycoconjugate J 15, 301–8 (1998).

    Google Scholar 

  109. Yip B, Chen SH, Mulder H, Hoppener JWM, Schachter H, Organization of the human beta-1,2-N-acetylglucosaminyltransferase I gene (MGAT1), which controls complex and hybrid N-glycan synthesis, Biochem J 321, 465–74 (1997).

    Google Scholar 

  110. Zhang W, Revers L, Pierce M, Schachter H, Regulation of expression of the human beta-1,2-N-acetylglucosaminyltransferase II gene (MGAT2) by Ets transcription factors, Biochem J 347, 511–8 (2000).

    Google Scholar 

  111. Buckhaults P, Chen L, Fregien N, Pierce M, Transcriptional regulation of N-acetylglucosaminyltransferase V by the src oncogene, J Biol Chem 272, 19575–81 (1997).

    Google Scholar 

  112. Carchon H, Van Schaftingen E, Matthijs G, Jaeken J, Carbohydrate-deficient glycoconjugate syndrome Type IA (phosphomannomutase deficiency), Biochim Biophys Acta 1455, 155–65 (1999).

    Google Scholar 

  113. Freeze HH, Aebi M, Molecular basis of carbohydrate-deficient glycoprotein syndromes Type I with normal phosphomannomutase activity, Biochim Biophys Acta 1455, 167–78 (1999).

    Google Scholar 

  114. Schachter H, Jaeken J, Carbohydrate-Deficient Glycoprotein Syndrome Type II, Biochim Biophys Acta 1455, 179–92 (1999).

    Google Scholar 

  115. Jaeken J, Vanderschueren-Lodeweyckx M, Casaer P, Snoeck L, Corbeel L, Eggermont E, Eeckels R, Familial psychomotor retardation with markedly fluctuating serum prolactin, FSH and GH levels, partial TBG deficiency, increased serum arylsulphatase A and increased CSF protein: a new syndrome? Pediatric Res 14, 179 (1980).

    Google Scholar 

  116. Jaeken J, Schachter H, Carchon H, De Cock P, Coddeville B, Spik G, Carbohydrate deficient Glycoprotein syndrome type II: A deficiency in Golgi localised N-acetylglucosaminyltransferase II, Arch Dis Child 71, 123–7 (1994).

    Google Scholar 

  117. Jaeken J, Spik G, Schachter H, Carbohydrate-deficient glycoprotein syndrome Type II: an autosomal recessive disease due to mutations in the N-acetylglucosaminyltransferase II gene. In Glycoproteins and Disease, edited by Montreuil J, Vliegenthart JFG, Schachter H, Vol. 30 (Elsevier, Amsterdam, The Netherlands, 1996), pp. 457–67.

    Google Scholar 

  118. Coddeville B, Carchon H, Jaeken J, Briand G, Spik G, Determination of glycan structures and molecular masses of the glycovariants of serum transferrin from a patient with carbohydrate deficient syndrome type II, Glycoconjugate J 15, 265–73 (1998).

    Google Scholar 

  119. Charuk JHM, Tan J, Bernardini M, Haddad S, Reithmeier RAF, Jaeken J, Schachter H, Carbohydrate-deficient glycoprotein syndrome type II--An autosomal recessive N-acetylglucosaminyltransferase II deficiency different from typical hereditary erythroblastic multinuclearity, with a positive acidified-serum lysis test (HEMPAS), Eur J Biochem 230, 797–805 (1995).

    Google Scholar 

  120. Tan J, Dunn J, Jaeken J, Schachter H, Mutations in the MGAT2 gene controlling complex N-glycan synthesis cause carbohydrate-deficient glycoprotein syndrome type II, an autosomal recessive disease with defective brain development, Am J Hum Genet 59, 810–7 (1996).

    Google Scholar 

  121. Pownall S, Kozak CA, Schappert K, Sarkar M, Hull E, Schachter H, Marth JD, Molecular cloning and characterization of the mouse UDP-N-acetylglucosamine: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I gene, Genomics 12, 699–704 (1992).

    Google Scholar 

  122. Marth JD, Will the transgenic mouse serve as a rosetta stone to glycoconjugate function, Glycoconjugate J 11, 3–8 (1994).

    Google Scholar 

  123. Metzler M, Gertz A, Sarkar M, Schachter H, Schrader JW, Marth JD, Complex asparagine-linked oligosaccharides are required for morphogenic events during post-implantation development, EMBO J 13, 2056–65 (1994).

    Google Scholar 

  124. Campbell RM, Metzler M, Granovsky M, Dennis JW, Marth JD, Complex asparagine-linked oligosaccharides in Mgat1-null embryos, Glycobiology 5, 535–43 (1995).

    Google Scholar 

  125. Granovsky M, Fode C, Warren CE, Campbell RM, Marth JD, Pierce M, Fregien N, Dennis JW, GlcNAc-transferase Vand core 2 GlcNAc-transferase expression in the developing mouse embryo, Glycobiology 5, 797–806 (1995).

    Google Scholar 

  126. Hennet T, Hagen FK, Tabak LA, Marth JD, T-cell-specific deletion of a polypeptide N-acetylgalactosaminyltransferase gene by site-directed recombination, Proc Natl Acad Sci USA 92, 12070–4 (1995).

    Google Scholar 

  127. Varki A, Marth J, Oligosaccharides in vertebrate development, Seminars in Developmental Biology 6, 127–38 (1995).

    Google Scholar 

  128. Marth JD, Complexity in O-linked oligosaccharide biosynthesis engendered by multiple polypeptide N-acetylgalactosaminyltransferases, Glycobiology 6, 701–5 (1996).

    Google Scholar 

  129. Priatel JJ, Sarkar M, Schachter H, Marth JD, Isolation, characterization and inactivation of the mouse Mgat3 gene: The bisecting N-acetylglucosamine in asparagine-linked oligosaccharides appears dispensable for viability and reproduction, Glycobiology 7, 45–56 (1997).

    Google Scholar 

  130. Chui D, OhEda M, Liao YF, Panneerselvam K, Lal A, Marek KW, Freeze HH, Moremen KW, Fukuda MN, Marth JD, Alphamannosidase-ll deficiency results in dyserythropoiesis and unveils an alternate pathway in oligosaccharide biosynthesis, Cell 90, 157–67 (1997).

    Google Scholar 

  131. Campbell R, Tan J, Schachter H, Bendiak B, Marth J, Targeted inactivation of the murine UDP-GlcNAc: alpha-6-D-mannoside beta-1,2-N-acetylglucosaminyltransferase II gene, Glycobiology 7, 1050 (1997).

    Google Scholar 

  132. Hennet T, Chui D, Paulson JC, Marth JD, Immune regulation by the ST6Gal sialyltransferase, Proc Natl Acad Sci USA 95, 4504–9 (1998).

    Google Scholar 

  133. Ellies LG, Tsuboi S, Petryniak B, Lowe JB, Fukuda M, Marth JD, Core 2 oligosaccharide biosynthesis distinguishes between selectin ligands essential for leukocyte homing and inflammation, Immunity 9, 881–90 (1998).

    Google Scholar 

  134. Marek KW, Vijay IK, Marth JD, A recessive deletion in the GlcNAc-1-phosphotransferase gene results in peri-implantation embryonic lethality, Glycobiology 9, 1263–71 (1999).

    Google Scholar 

  135. Priatel JJ, Chui D, Hiraoka N, Simmons CJ, Richardson KB, Page DM, Fukuda M, Varki NM, Marth JD, The ST3Gal-I sialyltransferase controls CD8+ T lymphocyte homeostasis by modulating O-glycan biosynthesis, Immunity 12, 273–83 (2000).

    Google Scholar 

  136. Shafi R, Iyer SP, Ellies LG, O'Donnell N, Marek KW, Chui D, Hart GW, Marth JD, The O-GlcNAc transferase gene resides on the X chromosome and is essential for embryonic stem cell viability and mouse ontogeny, Proc Natl Acad Sci USA 97, 5735–9 (2000).

    Google Scholar 

  137. Wang Y, Tan J, Campbell RM, Ditto D, Le D, Schachter H, Marth JD, Investigating a model of human CDG type II reveals a heterogenic disease with cell type-specific defects and frequent peri-natal lethality, Glycobiology 10, 1131–2 (2000).

    Google Scholar 

  138. Ioffe E, Stanley P, Mice lacking N-acetylglucosaminyltransferase I activity die at mid-gestation, trevealing an essential role for complex or hybrid N-linked carbohydrates, Proc Natl Acad Sci USA 91, 728–32 (1994).

    Google Scholar 

  139. Ioffe E, Liu Y, Stanley P, Complex N-glycans in Mgat1 null preimplantation embryos arise from maternal Mgat1 RNA, Glycobiology 7, 913–9 (1997).

    Google Scholar 

  140. Ishibashi K, Nishikawa A, Hayashi N, Kasahara A, Sato N, Fujii S, Kamada T, Taniguchi N, N-acetylglucosaminyltransferase III in human serum, and liver and hepatoma tissues: Increased activity in liver cirrhosis and hepatoma patients, Clin Chim Acta 185, 325–32 (1989).

    Google Scholar 

  141. Miyoshi E, Nishikawa A, Ihara Y, Gu J, Sugiyama T, Hayashi N, Fusamoto H, Kamada T, Taniguchi N, N-acetylglucosaminyltransferase III and V messenger RNA levels in LEC rats during hepatocarcinogenesis, Cancer Res 53, 3899–902 (1993).

    Google Scholar 

  142. Narasimhan S, Schachter H, Rajalakshmi S, Expression of N-acetylglucosaminyltransferase III in hepatic nodules during rat liver carcinogenesis promoted by orotic acid, J Biol Chem 263, 1273–81 (1988).

    Google Scholar 

  143. Nishikawa A, Gu J, Fujii S, Taniguchi N, Determination of N-acetylglucosaminyltransferases III, IV and V in normal and hepatoma tissues of rats, Biochim Biophys Acta Gen Subj 1035, 313–8 (1990).

    Google Scholar 

  144. Yoshimura M, Nishikawa A, Ihara Y, Nishiura T, Nakao H, Kanayama Y, Matuzawa Y, Taniguchi N, High expression of UDP-N-acetylglucosamine: beta-D mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) in chronic myelogenous leukemia in blast crisis, Int J Cancer 60, 443–9 (1995).

    Google Scholar 

  145. Yoshimura M, Ihara Y, Taniguchi N, Changes of beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) in patients with leukaemia, Glycoconjugate J 12, 234–40 (1995).

    Google Scholar 

  146. Aoyagi Y, Mori S, Naitoh A, Yanagi M, Suzuki Y, Suda T, Isokawa O, Igarashi H, Takahashi T, Isemura M, Asakura H, Alpha-fetoprotein-producing renal cell carcinoma with increased activity of N-acetylglucosaminyltransferase III, Nephron 74, 409–14 (1996).

    Google Scholar 

  147. Bhaumik M, Harris T, Sundaram S, Johnson L, Guttenplan J, Rogler C, Stanley P, Progression of hepatic neoplasms is severely retarded in mice lacking the bisecting N-acetylglucosamine on N-glycans: Evidence for a glycoprotein factor that facilitates hepatic tumor progression, Cancer Res 58, 2881–7 (1998).

    Google Scholar 

  148. Granovsky M, Fata J, Pawling J, Muller WJ, Khokha R, Dennis JW, Suppression of tumor growth and metastasis in Mgat5-deficient mice, Nat Med 6, 306–12 (2000).

    Google Scholar 

  149. Chen SH, Zhou SH, Sarkar M, Spence AM, Schachter H, Expression of three Caenorhabditis elegans N-acetylglucosaminyltransferase I genes during development, J Biol Chem 274, 288–97 (1999).

    Google Scholar 

  150. Chen S, Spence AM, Schachter H, Phenotypes of Caenorhabditis elegans UDP-GlcNAc: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I (GnT I) null mutants, Glycobiology 10, 1114 (2000).

    Google Scholar 

  151. Tan J, Chen S, Spence AM, Schachter H, Cloning and expression of Caenorhabditis elegans UDP-GlcNAc: alpha-6-D-mannoside beta-1,2-N-acetylglucosaminyltransferase II (GnT II), Glycobiology 10, 1115 (2000).

    Google Scholar 

  152. Sarkar M, Schachter H, Cloning and expression of Drosophila melanogaster UDP-GlcNAc: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I, Glycobiology 10, 1114–5 (2000).

    Google Scholar 

  153. Betel D, Zhang W, Schachter H, Human UDP-GlcNAc: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I.2 (GnT I.2), a homologue of GnT I, is enzymatically active, Glycobiology 10, 1103–4 (2000).

    Google Scholar 

  154. Gastinel LN, Cambillau C, Bourne Y, Crystal structures of the bovine beta-4-galactosyltransferase catalytic domain and its complex with uridine diphosphogalactose, EMBO J 18, 3546–57 (1999).

    Google Scholar 

  155. Ñnligil UM, Zhou S, Yuwaraj S, Sarkar M, Schachter H, Rini JM, X-ray crystal structure of rabbit N-acetylglucosaminyltransferase I, a key enzyme in the biosynthesis of N-linked glycans, Glycobiology 9, 1102 (1999).

    Google Scholar 

  156. Ñnligil UM, Zhou S, Yuwaraj S, Sarkar M, Schachter H, Rini JM, X-ray crystal structure of rabbit N-acetylglucosaminyltransferase I: catalytic mechanism and a newprotein superfamily, EMBOJ 19, 5269–80 (2000).

    Google Scholar 

  157. Sarkar M, Schachter H, Expression of UDP-GlcNAc:?3-D-mannoside ?-1,2-N-Acetylglucosaminyltransferase I (GnT I) in insect cells, Glycobiology 2, 483 (1992).

    Google Scholar 

  158. Sarkar M, Expression of recombinant rabbit UDP-GlcNAc: alpha 3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I catalytic domain in Sf9 insect cells, Glycoconjugate J 11, 204–9 (1994).

    Google Scholar 

  159. Sarkar M, Pagny S, Unligil U, Joziasse D, Mucha J, Glossl J, Schachter H, Removal of 106 amino acids from the N-terminus of UDP-GlcNAc: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I does not inactivate the enzyme, Glycoconjugate J 15, 193–7 (1998).

    Google Scholar 

  160. Schachter H, McGuire EJ, Roseman S, Sialic acids. XIII.Auridine diphosphate D-galactose: mucin galactosyltransferase from porcine submaxillary gland, J Biol Chem 246, 5321–8 (1971).

    Google Scholar 

  161. Williams D, Schachter H, Mucin synthesis. I. Detection in canine submaxillary glands of an N-acetylglucosaminyltransferase which acts on mucin substrates, J Biol Chem 255, 11247–52 (1980).

    Google Scholar 

  162. Williams D, Longmore GD, Matta KL, Schachter H, Mucin synthesis. II. Substrate specificity and product identification studies on canine submaxillary gland UDP-GlcNAc: Gal?1-3GalNAc (GlcNAc to GalNAc) ?6-N-acetylglucosaminyltransferase, J Biol Chem 255, 11253–61 (1980).

    Google Scholar 

  163. Schachter H, Brockhausen I, The biosynthesis of serine(threonine)-N-acetylgalactosamine-linked carbohydrate moieties. In Glycoconjugates. Composition, Structure and Function, edited by Allen HJ, Kisailus EC, (Marcel Dekker, Inc., New York, NY, 1992), pp. 263–332.

    Google Scholar 

  164. Schachter H, Brockhausen I, The biosynthesis of branched Oglycans. In Mucus and Related Topics, edited by Chantler E, Ratcliffe NA, The Society for Experimental Biology, Vol. 43 (Cambridge, England, 1989), pp. 1–26.

    Google Scholar 

  165. Brockhausen I, Biosynthesis of O-glycans of the N-acetylgalactosamine-?-Ser/Thr linkage type. In Glycoproteins, edited by Montreuil J, Vliegenthart JFG, Schachter H, Vol. 29a (Elsevier, Amsterdam, The Netherlands, 1995), pp. 201–59.

    Google Scholar 

  166. Brockhausen I, Williams D, Matta KL, Orr J, Schachter H, Mucin synthesis. III. UDP-GlcNAc: Gal?1-3(GlcNAc?1-6)Gal-NAc-R (GlcNAc to Gal) ?3-N-acetylglucosaminyltransferase, an enzyme in porcine gastric mucosa involved in the elongation of mucin-type oligosaccharides, Can J Biochem Cell Biol 61, 1322–33 (1983).

    Google Scholar 

  167. Brockhausen I, Rachaman ES, Matta KL, Schachter H, Mucin Synthesis. IV. The separation by high performance liquid chromatography of phenyl, benzyl and ortho-nitrophenyl oligosaccharide glycosides. Analysis of substrates and products for four N-acetyl-D-glucosaminyl-transferases involved in mucin synthesis, Carbohydrate Res 120, 3–16 (1983).

    Google Scholar 

  168. Brockhausen I, Matta KL, Orr J, Schachter H, Mucin synthesis. VI. UDP-GlcNAc: GalNAc-R ?3-N-acetylglucosaminyltransferase and UDP-GlcNAc: GlcNAc?1-3GalNAc-R (GlcNAc to GalNAc) ?6-N-acetylglucosaminyltransferase from pig and rat colon mucosa, Biochemistry 24, 1866–74 (1985).

    Google Scholar 

  169. Brockhausen I, Orr J, Schachter H, Mucin synthesis. V. The action of pig gastric mucosal UDP-GlcNAc: Gal?1-3(R1)Gal-NAc-R2 (GlcNAc to Gal) ?3-N-acetylglucosaminyltransferase on high molecular weight substrates, Can J Biochem Cell Biol 62, 1081–90 (1984).

    Google Scholar 

  170. Brockhausen I, Matta KL, Orr J, Schachter H, Koenderman AHL, van den Eijnden DH, Mucin synthesis. VII. Conversion of R1-?1-3Gal-R2 to R1-?1-3(GlcNAc?l-6)Gal-R2 and of R1-?1-3GalNAc-R2 to R1-?1-3(GlcNAc?1-6)GalNAc-R2 by a ?6-N-acetylglucosaminyltransferase in pig gastric mucosa, Eur J Biochem 157, 463–74 (1986).

    Google Scholar 

  171. Yang J, Bhaumik M, Liu Y, Stanley P, Regulation of N-linked glycosylation. Neuronal cell-specific expression of a 5' extended transcript from the gene encoding N-acetylglucosaminyltransferase I, Glycobiology 4, 703–12 (1994).

    Google Scholar 

  172. Kumar R, Yang J, Eddy RL, Byers MG, Shows TB, Stanley P, Cloning and expression of the murine gene and chromosomal location of the human gene encoding N-acetylglucosaminyltransferase I, Glycobiology 2, 383–93 (1992).

    Google Scholar 

  173. Fukada T, Iida K, Kioka N, Sakai H, Komano T, Cloning of a cDNA Encoding N-Acetylglucosaminyltransferase I from Rat Liver and Analysis of Its Expression in Rat Tissues, Biosci Biotechnol Biochem 58, 200–1 (1994).

    Google Scholar 

  174. Narasimhan S, Yuen R, Fode CJ, Ali J, Rajalakshmi S, Schappert K, Dennis JW, Schachter H, Cloning of cDNA encoding chicken beta-1,2-N-acetylglucosaminyltransferase I, Glycobiology 3, 531 (1993).

  175. Mucha J, Kappel S, Schachter H, Hane W, Glössl J, Molecular cloning and characterization of cDNAs coding for N-acetylglucosaminyltransferases I and II from Xenopus laevis ovary, Glycoconjugate Journal 12, 473 (1995).

    Google Scholar 

  176. Puthalakath H, Burke J, Gleeson PA, Glycosylation defect in Lec1 Chinese hamster ovary mutant is due to a point mutation in N-acetylglucosaminyltransferase I gene, J Biol Chem 271, 27818–22 (1996).

    Google Scholar 

  177. Opat AS, Puthalakath H, Burke J, Gleeson PA, Genetic defect in N-acetylglucosaminyltransferase I gene of a ricin-resistant baby hamster kidney mutant, Biochem J 336, 593–8 (1998).

    Google Scholar 

  178. Leeb T, Kriegesmann B, Baumgartner BG, Klett C, Yerle M, Hameister H, Brenig B, Molecular cloning of the porcine beta-1,2-N-acetylglucosaminyltransferase II gene and assignment to chromosome 1q23–q27,, Bba Gen Subjects 1336, 361–6 (1997).

    Google Scholar 

  179. Ihara Y, Nishikawa A, Tohma T, Soejima H, Niikawa N, Taniguchi N, cDNA cloning, expression, and chromosomal localization of human N-acetylglucosaminyltransferase III (GnTIII), J Biochem 113, 692–8 (1993).

    Google Scholar 

  180. Bhaumik M, Seldin MF, Stanley P, Cloning and chromosomal mapping of the mouse Mgat3 gene encoding N-acetylglucosaminyltransferase III, Gene 164, 295–300 (1995).

    Google Scholar 

  181. Minowa MT, Oguri S, Yoshida A, Hara T, Iwamatsu A, Ikenaga H, Takeuchi M, cDNA cloning and expression of bovine UDP-Nacetylglucosamine: alpha 1,3-D-mannoside beta 1,4-N-acetylglucosaminyltransferase IV, J Biol Chem 273, 11556–62 (1998).

    Google Scholar 

  182. Yoshida A, Minowa MT, Takamatsu S, Hara T, Oguri S, Ikenaga H, Takeuchi M, Tissue specific expression and chromosomal mapping of a human UDP-N-acetylglucosamine: alpha 13-D-mannoside beta 14-N-acetylglucosaminyltransferase, Glycobiology 9, 303–10 (1999).

    Google Scholar 

  183. Saito H, Nishikawa A, Gu JG, Ihara Y, Soejima H, Wada Y, Sekiya C, Niikawa N, Taniguchi N, CDNA Cloning and Chromosomal Mapping of Human N-Acetylglucosaminyltransferase V, Biochem Biophys Res Commun 198, 318–27 (1994).

    Google Scholar 

  184. Shoreibah M, Perng GS, Adler B, Weinstein J, Bas R, Cupples R, Wen D, Browne JK, Buckhaults P, Fregien N, Pierce M, Isolation, characterization, and expression of a cDNA encoding Nacetylglucosaminyltransferase V, J Biol Chem 268, 15381–5 (1993).

    Google Scholar 

  185. Weinstein J, Sundaram S, Wang XH, Delgado D, Basu R, Stanley P, A point mutation causes mistargeting of Golgi GlcNAc-TV in the Lec4A Chinese hamster ovary glycosylation mutant, J Biol Chem 271, 27462–9 (1996).

    Google Scholar 

  186. Sakamoto Y, Taguchi T, Honke K, Korekane H, Watanabe H, Tano Y, Dohmae N, Takio K, Horii A, Taniguchi N, Molecular cloning and expression of cDNA encoding chicken UDP-GlcNAc: GlcNAc-beta-1,6(GlcNAc-beta-1,2)Man-alpha-1-R[GlcNAc to Man] beta-1,4-N-acetylglucosaminyltransferase VI, J Biol Chem 275, In press (2000).

  187. Taguchi T, Ogawa T, Inoue S, Inoue Y, Sakamoto Y, Korekane H, Taniguchi N, Purification and characterization of UDP-GlcNAc: GlcNAc-beta-1,6(GlcNAc-beta-1,2)Man-alpha-1-R[GlcNAc to Man] beta-1,4-N-acetylglucosaminyltransferase VI from hen oviduct, J Biol Chem 275, 32598–602 (2000).

    Google Scholar 

  188. Taguchi T, Kitajima K, Inoue S, Inoue Y, Yang JM, Schachter H, Brockhausen I, Activity of UDP-GlcNAc: GlcNAc beta 1?6(GlcNAc beta 1?2)Man alpha 1?R[GlcNAc to Man]beta 1?4N-acetylglucosaminyltransferase VI (GnT VI) from the ovaries of Oryzias latipes (Medaka fish), Biochem Biophys Res Commun 230, 533–6 (1997).

    Google Scholar 

  189. Lawford GR, Schachter H, Biosynthesis of glycoprotein by liver. The incorporation in vivo of C-14-glucosamine into proteinbound hexosamine and sialic acid of rat liver subcellular fractions, J Biol Chem 241, 5408–18 (1966).

    Google Scholar 

  190. Hudgin RL, Schachter H, Porcine sugar nucleotide: glycoprotein glycosyltransferases. III. Blood serum and liver N-acetylglucosaminyltransferase, Can J Biochem 49, 847–52 (1971).

    Google Scholar 

  191. Jabbal I, Schachter H, Pork liver guanosine diphosphate-Lfucose glycoprotein fucosyltransferases, J Biol Chem 246, 5154–61 (1971).

    Google Scholar 

  192. Schachter H, Michaels MA, Tilley CA, Crookston MC, Crookston JH, Qualitative differences in the N-acetyl-D-galactosaminyltransferases produced by human A1 and A2 genes, Proc Nat Acad Sci USA 70, 220–4 (1973).

    Google Scholar 

  193. Kornblatt MJ, Schachter H, Murray RK, Partial characterization of a novel glycerogalactolipid from rat testis, Biochem Biophys Res Comm 48, 1489–94 (1972).

    Google Scholar 

  194. Kornblatt MJ, Knapp A, Levine M, Schachter H, Murray RK, Studies on the structure and formation during spermatogenesis of the sulfoglycerogalacto-lipid of rat testis, Can J Biochem 52, 689–97 (1974).

    Google Scholar 

  195. Wilson JR, Williams D, Schachter H, The control of glycoprotein synthesis. I. N-acetylglucosamine linkage to mannose residue as a signal for the attachment of L-fucose to the asparagine-linked N-acetylglucosamine residue of glycopeptide from a1-acid glycoprotein, Biochem Biophys Res Comm 72, 909–16 (1976).

    Google Scholar 

  196. Letts PJ, Meistrich ML, Bruce WR, Schachter H, Glycoprotein glycosyltransferase levels during spermatogensis in mice, Biochem Biophys Acta 343, 192–207 (1974).

    Google Scholar 

  197. Letts PJ, Hunt RC, Shirley MA, Pinteric L, Schachter H, Late spermatocytes from immature rat testis. Isolation, electron microscopy, lectin agglutinability and capacity for glycoprotein and sulfo galactoglycerolipid biosynthesis, Biochim Biophys Acta 541, 59–75 (1978).

    Google Scholar 

  198. Lombart C, Sturgess J, Schachter H, The effect of turpentineinduced inflammation on rat liver glycosyltransferase and Golgi complex ultrastructure, Biochim Biophys Acta 629, 1–12 (1980).

    Google Scholar 

  199. Lingwood C, Hay G, Schachter H, Tissue distribution of sulfolipids in the rat. Restricted location of sulfatoxygalactosyl-acylalkylglycerol, Can J Biochem 59, 556–63 (1981).

    Google Scholar 

  200. Lingwood C, Schachter H, Localization of sulfatoxygalactosyl-acylalkylglycerol at the surface of rat testicular germinal cells by immunocytochemical techniques: pH dependence of a nonimmunological reaction between immunoglobulin and germinal cells, J Cell Biol 89, 621–30 (1981).

    Google Scholar 

  201. Paquet MR, Narasimhan S, Schachter H, Moscarello MA, Branch specificity of purified rat liver Golgi UDP-galactose: N-acetylglucosamine beta-1,4-galactosyltransferase. Preferential transfer of galactose on the GlcNAc beta 1,2-Man alpha 1,3-branch of a complex biantennary Asn-linked oligosaccharide, J Biol Chem 259, 4716–21 (1984).

    Google Scholar 

  202. Narasimhan S, Freed JC, Schachter H, The effect of a “bisecting” N-acetylglucosaminyl group on the binding of biantennary, complex oligosaccharides to concanavalin A, Phaseolus vulgaris erythroagglutinin (E-PHA), and Ricinus communis agglutinin (RCA-120) immobilized on agarose, Carbohydrate Research 149, 65–83 (1986).

    Google Scholar 

  203. Narasimhan S, Freed JC, Schachter H, Control of glycoprotein synthesis. Bovine milk UDPgalactose:N-acetylglucosamine beta-4-galactosyltransferase catalyzes the preferential transfer of galactose to the GlcNAc beta1,2Man alpha 1,3-branch of both bisected and nonbisected complex biantennary asparagine-linked oligosaccharides, Biochemistry 24, 1694–1700 (1985).

    Google Scholar 

  204. Kalsner I, Hintz W, Reid LS, Schachter H, Insertion into Aspergillus nidulans of functional UDP-GlcNAc: alpha 3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I, the enzyme catalysing the first commited step from oligomannose to hybrid and complex N-glycans, Glycoconjugate J 12, 360–70 (1995).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Structural Biology and Biochemistry, Research Institute, The Hospital for Sick Children, Faculty of Medicine, University of Toronto, 555 University Avenue, Toronto, Ont, M5G 1X8, Canada

    Harry Schachter MD, PhD, FRSC

Authors
  1. Harry Schachter MD, PhD, FRSC
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schachter, H. The joys of HexNAc. The synthesis and function of N-andO-glycan branches. Glycoconj J 17, 465–483 (2000). https://doi.org/10.1023/A:1011010206774

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1011010206774

Search

Navigation