Seminars in Pediatric Neurology
Volume 12, Issue 3 , Pages 134-143 , September 2005

Essentials of Glycosylation

  • Erik A. Eklund, MD, PhD
    • ,
  • Hudson H. Freeze, PhD

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Hudson H. Freeze, PhD, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037.

References 

  1. Freeze HH . Congenital disorders of glycosylation and the pediatric liver . Semin Liver Dis . 2001;21:501–515
  2. Wu X , Rush JS , Karaoglu D , et al.   Deficiency of UDP-GlcNAc:Dolichol Phosphate N-Acetylglucosamine-1 Phosphate Transferase (DPAGT1) causes a novel congenital disorder of Glycosylation Type Ij . Hum Mutat . 2003;22:144–150
  3. Imbach T , Schenk B , Schollen E , et al.   Deficiency of dolichol-phosphate-manose synthase-1 causes congenital disorder of glycosylation Ie . J Clin Invest . 2000;105:233–239
  4. Kranz C , Denecke J , Lehle L , et al.   Congenital disorder of glycosylation Ik (CDG-Ik) (a defect of mannosyltransferase I) . Am J Hum Genet . 2004;74:545–551
  5. Grubenmann CE , Frank CG , Hulsmeier AJ , et al.   Deficiency of the first mannosylation step in the N-glycosylation pathway causes congenital disorder of glycosylation type Ik . Hum Mol Genet . 2004;13:535–542
  6. Schwarz M , Thiel C , Lubbehusen J , et al.   Deficiency of GDP-Man (GlcNAc2-PP-dolichol mannosyltransferase causes congenital disorder of glycosylation type Ik) . Am J Hum Genet . 2004;74:472–481
  7. Thiel C , Schwarz M , Peng J , et al.   A new type of congenital disorders of glycosylation (CDG-Ii) provides new insights into the early steps of dolichol-linked oligosaccharide biosynthsis . J Biol Chem . 2003;278:22498–22505
  8. Kranz C , Denecke J , Lehrman MA , et al.   A mutation in the MPDU1 gene causes congenital disorder of glycosylation type If (CDG-If) . J Clin Invest . 2001;108:1613–1619
  9. Körner C , Knauer R , Stephani U , et al.   Carbohydrate deficient glycoprotein syndrome type IV (deficiency of dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase) . EMBO J . 1999;18:6816–6822
  10. Frank CG , Grubenmann CE , Eyaid W , et al.   Identification and functional analysis of a defect in the human ALG9 gene (definition of congenital disorder of glycosylation type IL) . Am J Hum Genet . 2004;75:146–150
  11. Chantret I , Dupre T , Delenda C , et al.   Congential disorder of glycosylation type Ig is defined by a deficiency in dolichyl-P-mannose (Man7GlcNAc2-PP-dolichyl mannosyltransferase) . J Biol Chem . 2002;277:25815–25822
  12. Körner C , Knauer R , Holzbach U , et al.   Carbohydrate deficient glycoprotein syndrome type V (deficiency of dolichyl-P-Glc:Man9GlcNAc2-PP-dolichyl glucosyltransferase) . Proc Natl Acad Sci U S A . 1998;95:13200–13205
  13. Chantret I , Dancourt J , Dupre T , et al.   A deficiency in dolichyl-P-glucose (Glc1Man9GlcNAc2-PP-dolichyl alpha3-glucosyltransferase defines a new subtype of congenital disorders of glycosylation) . J Biol Chem . 2003;278:9962–9971
  14. Niehues R , Hasilik M , Alton G , et al.   Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy . J Clin Invest . 1998;101:1414–1420
  15. Van Schaftingen E , Jaeken J . Phosphomannomutase deficiency is a cause of carbohydrate-deficient glycoprotein syndrome type I . FEBS Lett . 1995;377:318–320
  16. De Praeter CM , Gerwig GJ , Bause E , et al.   A novel disorder caused by defective biosynthesis of N-linked oligosaccharides due to glucosidase I deficiency . Am J Hum Genet . 2000;66:1744–1756
  17. Tan J , Dunn J , Jaeken J , et al.   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 . 1996;59:810–817
  18. Lübke T , Marquardt T , Etzioni A , et al.   Complementation cloning identifies CDG-Iic, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency . Nat Genet . 2001;28:73–76
  19. Hansske B , Thiel C , Lübke T , et al.   Deficiency of UDP-galactose:N-acetylglucosamine beta-1,4-galactosyltransferase I causes the congenital disorder of glycosylation type IId . J Clin Invest . 2002;109:725–733
  20. Wu X , Steet RA , Bohorov O , et al.   Mutations of the COG complex subunit gene COG7 causes a lethal congenital disorder . Nat Med . 2004;10:518–523
  21. Martinez-Duncker I , Dupre T , Piller V , et al.   Genetic complementation reveals a novel human congenital disorder of glycosylation type II, due to inactivation of the Golgi CMP-sialic acid transporter . Blood . 2005;105:2671–2676
  22. Strahl-Bolsinger S , Gentzsch M , Tanner W . Protein O-mannosylation . Biochim Biophys Acta . 1999;1426:297–307
  23. Finne J , Krusius T , Margolis RK , et al.   Novel mannitol-containing oligosaccharides obtained by mild alkaline borohydride treatment of a chondroitin sulfate proteoglycan from the brain . J Biol Chem . 1979;254:10295–10300
  24. Endo T . Structure, function and pathology of O-mannosyl glycans . Glycoconj J . 2004;21:3–7
  25. Winder SJ . The complexities of dystroglycan . Trends Biochem Sci . 2001;26:118–124
  26. Martin-Rendon E , Blake DJ . Protein glycosylation in disease (new insights into the congenital muscular dystrophies) . Trends Pharmacol Sci . 2003;24:178–183
  27. Dalkilic I , Kunkel LM . Muscular dystrophies (gene to pathogenesis) . Curr Opin Genet Dev . 2003;13:231–238
  28. Manya H , Chiba A , Yoshida A , et al.   Demonstration of mammalian protein O-mannosyltransferase activity (coexpression of POMT1 and POMT2 required for enzymatic activity) . Proc Natl Acad Sci U S A . 2004;101:500–505
  29. Yoshida A , Kobayashi K , Manya H , et al.   Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferse, POMGnT1 . Dev Cell . 2001;1:717–724
  30. Beltran-Valero de Bernabe D , Currier S , Steinbrecher A , et al.   Mutations in the O-mannosyltransferase gene POMT1 give rise to the severe neuronal migration disorder Walker-Warburg syndrome . Am J Hum Genet . 2002;71:1033–1043
  31. van Reeuwijk J , Janssen M , van den Elzen C , et al.   POMT2 mutations cause alpha-dystroglycan hypoglycosylation and Walker Warburg syndrome . J Med Genet . 2005;42:907–912
  32. Grewal PK , Hewitt JE . Glycosylation defects (a new mechanism for muscular dystrophy?) . Hum Mol Genet . 2003;12:R259–R264
  33. Grewal PK , Holzfeind PJ , Bittner RE , et al.   Mutant glycosyltransferase and altered glycosylation of alpha-dystroglycan in the myodystrophy mouse . Nat Genet . 2001;28:151–154
  34. Kjellen L , Lindahl U . Proteoglycans (structures and interactions) . Annu Rev Biochem . 1991;60:443–475
  35. Bernfield M , Gotte M , Park PW , et al.   Functions of cell surface heparan sulfate proteoglycans . Annu Rev Biochem . 1999;68:729–777
  36. Iozzo RV . Matrix proteoglycans (from molecular design to cellular function) . Annu Rev Biochem . 1998;67:609–652
  37. Zak BM , Crawford BE , Esko JD . Hereditary multiple exostoses and heparan sulfate polymerization . Biochim Biophys Acta . 2002;1573:346–355
  38. McCormick C , Leduc Y , Martindale D , et al.   The putative tumour suppressor EXT1 alters the expression of cell-surface heparan sulfate . Nat Genet . 1998;19:158–161
  39. Lin X , Wei G , Shi Z , et al.   Disruption of gastrulation and heparan sulfate biosynthesis in EXT1-deficient mice . Dev Biol . 2000;224:299–311
  40. Quentin E , Gladen A , Roden L , et al.   A genetic defect in the biosynthesis of dermatan sulfate proteoglycan (galactosyltransferase I deficiency in fibroblasts from a patient with a progeroid syndrome) . Proc Natl Acad Sci U S A . 1990;87:1342–1346
  41. Tettamanti G . Ganglioside/glycosphingolipid turnover (new concepts) . Glycoconj J . 2004;20:301–317
  42. Hakomori S . Glycosphingolipids in cellular interaction, differentiation, and oncogenesis . Annu Rev Biochem . 1981;50:733–764
  43. Simpson MA , Cross H , Proukakis C , et al.   Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase . Nat Genet . 2004;36:1225–1229
  44. Schuette CG , Doering T , Kolter T , et al.   The glycosphingolipidoses—from disease to basic principles of metabolism . Biol Chem . 1999;380:759–766
  45. Burda P , Aebi M . The dolichol pathway of N-glycosylation . Biochim Biophys Acta . 1999;1426:239–257
  46. Marquardt T , Freeze H . Congenital disorders of glycosylation (glycosylation defects in man and biological models for their study) . Biol Chem . 2001;382:161–177
  47. Winther JR , Stevens TH , Kielland-Brandt MC . Yeast carboxypeptidase Y requires glycosylation for efficient intracellular transport, but not for vacuolar sorting, in vivo stability, or activity . Eur J Biochem . 1991;197:681–689
  48. Imbach T , Burda P , Kuhnert P , et al.   A mutation in the human ortholog of Saccharomyces cerevisiae ALG6 gene causes carbohydrate-deficient glycoprotein syndrome type-Ic . Proc Natl Acad Sci U S A . 1999;96:6982–6987
  49. Grubenmann CE , Frank CG , Kjaergaard S , et al.   ALG12 mannosyltransferease defect in congenital disorder of glycosylation type Ig . Hum Mol Genet . 2002;11:2331–2339
  50. Stanley P . Glycosylation mutants of animal cells . Annu Rev Genet . 1984;18:525–552
  51. Kingsley DM , Kozarsky KF , Segal M , et al.   Three types of low denisty lipoprotein receptor-deficient mutants have pleiotropic defects in the synthesis of N-linked, O-linked, and lipid-linked carbohydrate chains . J Cell Biol . 1986;102:1576–1585
  52. Schenk B , Imbach T , Frank CG , et al.   MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If . J Clin Invest . 2001;108:1687–1695
  53. Ray MK , Yang J , Sundaram S , et al.   A novel glycosylation phenotype expressed by Lec23, a Chinese hamster ovary mutant deficient in alpha-glucosidase I . J Biol Chem . 1991;266:22818–22825
  54. Hong Y , Sundaram S , Shin DJ , et al.   The Lec23 Chinese hamster ovary mutant is a sensitive host for detecting mutations in alpha-glucosidase I that give rise to congenital disorder of glycosylation IIb (CDG IIb) . J Biol Chem . 2004;279:49894–49901
  55. Deutscher SL , Nuwayhid N , Stanley P , et al.   Translocation across Golgi vesicle membranes (a CHO glycosylation mutant deficient in CMP-sialic acid transport) . Cell . 1984;39:295–299
  56. Rosenwald AG , Stanley P , McLachlan KR , et al.   Mutants in dolichol synthesis (conversion of polyprenol to dolichol appears to be a rae-limiting step in dolichol synthesis) . Glycobiology . 1993;3:481–488
  57. Ohkura T , Fukushima K , Kurisaki A , et al.   A partial deficiency of dehydrodolichol reduction is a cause of carbohydrate-deficient glycoprotein syndrome type I . J Biol Chem . 1997;272:6868–6875
  58. Trowbridge IS , Hyman R , Ferson T , et al.   Expression of Thy-1 glycoprotein on lectin-resistant lymphoma cell lines . Eur J Immunol . 1978;8:716–723
  59. Sauer B , Henderson N . Cre-stimulated recombination at loxP-containing DNA sequences placed into the mammalian genome . Nucleic Acids Res . 1989;17:147–161
  60. Marek KW , Vijay IK , Marth JD . A recessive deletion in the G1cNAc-1-phosphotransferase gene results in peri-implantation embryonic lethality . Glycobiology . 1999;9:1263–1271
  61. Derossi C , Bode L , Eklund EA , et al.   Ablation of mouse phosphomannose isomerase (Mpi) causes mannose-6-phosphate accumulation, toxicity, and embryonic lethality . J Biol Chem . 2005;16339137; [Epub ahead of print] PMID
  62. Kornfeld R , Kornfeld S . Assembly of asparagine-linked oligosaccharides . Annu Rev Biochem . 1985;54:631–664
  63. Ioffe E , Stanley P . Mice lacking N-acetylglucosaminyltransferase I activity die at mid-gestation, revealing an essential role for complex or hybrid N-linked carbohydrates . Proc Natl Acad Sci U S A . 1994;91:728–732
  64. Chui D , Oh-Eda M , Liao YF , et al.   Alpha-mannosidase-II deficiency results on dyserythropoiesis and unveils an alternate pathway in oligosaccharide biosynthesis . Cell . 1997;90:157–167
  65. Fukuda MN , Masri KA , Dell A , et al.   Incomplete synthesis of N-glycans in congenital dyserythropoietic anemia type II caused by a defect in the gene encoding alpha-mannosidase II . Proc Natl Acad Sci U S A . 1990;87:7443–7447
  66. Akama TO , Nakagawa H , Sugihara K , et al.   Germ cell survival through carbohydrate-mediated interaction with Sertoli cells . Science . 2002;295:124–127
  67. Schachter H . The ‘yellow brick road’ to branched complex N-glycans . Glycobiology . 1991;1:453–461
  68. Wang Y , Schachter H , Marth JD . Mice with a homozygous deletion of the Mgat2 gene encoding UDP-N-acteylglucosamine:alpha-6-D-mannoside beta1,2-N-acetylglucosaminyltransferase II (a model for congenital disorder of glycosylation type IIa) . Biochim Biophys Acta . 2002;1573:301–311
  69. Jaeken J , Schachter H , Carchon H , et al.   Carbohydrate deficient glycoprotein syndrome type II (a deficiency in Golgi localised N-acetylglucosaminyltransferase II) . Arch Dis Child . 1994;71:123–127
  70. Asano M , Furukawa K , Kido M , et al.   Growth retardation and early death of beta-1,4-galactosyltransferase knockout mice with augmented proliferation and abnormal differentiation of epithelial cells . EMBO J . 1997;16:1850–1857
  71. Sperandio M , Thatte A , Foy D , et al.   Severe impairment of leukocyte rolling in venules of core 2 glucosyltransferase-deficient mice . Blood . 2001;97:3812–3819
  72. Maly P , Thall A , Petryniak B , et al.   The alpha(1,3)fucosyltransferase Fuc-TVII controls leukocyte trafficking through an essential role in L-, E-, and P-selectin ligand biosynthesis . Cell . 1996;86:643–653
  73. Bengtson P , Larson C , Lundblad A , et al.   Identification of a missense mutation (G329A;Arg(110)→Gln) in the FUT7 gene . J Biol Chem . 2001;276:31575–31582
  74. Topaz O , Shurman DL , Bergman R , et al.   Mutations in GALNT3, encoding a protein inolved in O-linked glycosylation, cause familial tumoral calcinosis . Nat Genet . 2004;36:579–581
  75. Willer T , Prados B , Falcon-Perez JM , et al.   Targeted disruption of the Walker-Warburg syndrome gene Pomt1 in mouse results in embryonic lethality . Proc Natl Acad Sci U S A . 2004;101:14126–14131
  76. Yamashita T , Hashiramoto A , Haluzik M , et al.   Enhanced insulin sensitivity in mice lacking ganglioside GM3 . Proc Natl Acad Sci U S A . 2003;100:3445–3449
  77. Yamashita T , Wu YP , Sandhoff R , et al.   Interruption of ganglioside synthesis produces central nervous system degeneration and altered axon-glial interactions . Proc Natl Acad Sci U S A . 2005;102:2725–2730
  78. Inatani M , Irie F , Plump AS , et al.   Mammalian brain morphogenesis and midline axon guidance require heperan sulfate . Science . 2003;302:1044–1046
  79. Forsberg E , Kjellen L . Heparan sulfate (lessons from knockout mice) . J Clin Invest . 2001;108:175–180
  80. McAlindon TE , Biggee BA . Nutritional factors and osteoarthritis (recent developments) . Curr Opin Rheumatol . 2005;17:647–652
  81. Marquardt T , Denecke J . Congenital disorders of glycosylation (review of their molecular bases, clinical presentations and specific therapies) . Eur J Pediatr . 2003;162:359–379
  82. Vogt G , Chapgier A , Yang K , et al.   Gains of glycosylation comprise an unexpectedly large group of pathogenic mutations . Nat Genet . 2005;37:692–700
  83. Stenson PD , Ball EV , Mort M , et al.   Human Gene Mutation Database (HGMD) (2003 update) . Hum Mutat . 2003;21:577–581
  84. Aly AM , Higuchi M , Kasper CK , et al.   Hemophilia A due to mutations that create new N-glycosylation sites . Proc Natl Acad Sci U S A . 1992;89:4933–4937
  85. Lonnqvist L , Karttunen L , Rantamaki T , et al.   A point mutation creating an extra N-glycosylation site in fibrillin-1 results in neonatal Marfan syndrome . Genomics . 1996;36:468–475
  86. Hammerle MM , Aleksandrov AA , Chang XB , et al.   A novel CFTR disease-associated mutation causes addition of an extra N-linked oligosaccharide . Glycoconj J . 2000;17:807–813

 Supported by the National Institutes for Health Grants DK55615 and DK0650691 to HHF and postdoctoral fellowship from STINT/VR (Sweden) to EAE.

 Dr. Erik A. Eklund’s present address is Lund University, Dept. for Cell and Molecular Biology, BMC C13, 221 84 Lund, Sweden. Email: Erik.Eklund@med.lu.se.

PII: S1071-9091(05)00077-X

doi: 10.1016/j.spen.2005.11.001

Seminars in Pediatric Neurology
Volume 12, Issue 3 , Pages 134-143 , September 2005

Article Tools

* Image Usage & Resolution