Polysialylation of NCAM

  • Herbert Hildebrandt
  • Martina Mühlenhoff
  • Rita Gerardy-SchahnEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 663)


A unique feature of the neural cell adhesion molecule NCAM is that it can be decorated with polysialic acid, a large negatively charged and highly hydrated glycan, which acts as a key regulator of NCAM-mediated and other cell surface interactions. Here, we give a brief overview of the regulation of polysialic acid expression in ontogenesis and tumor development and highlight the interplay of the polysialyltransferases ST8SiaII and ST8SiaIV in implementing the biosynthesis of this unusual carbohydrate polymer. In particular, we focus on recent advances in the separate or combined genetic ablation of the two enzymes, which reveal its vital role in brain development and provide insights into the vigorous control and the structural complexity of NCAM polysialylation.


Polysialic acid Neural cell adhesion molecule NCAM Polysialyltransferases Cell surface glycosylation Tumorigenesis Brain development 



The authors thank Deutsche Forschungsgemeinschaft (to RGS, MM, HH), the Deutsche Krebshilfe (to MM and HH), and PROMEMORIA EC FP6 (to RGS) for having given financial support through grants to do this work.


  1. 1.
    Fujimoto I, Bruses JL, Rutishauser U (2001) Regulation of cell adhesion by polysialic acid: effects on cadherin, IgCAM and integrin function and independence from NCAM binding or signaling activity. J Biol Chem 276:31745-31751PubMedGoogle Scholar
  2. 2.
    Johnson CP, Fragneto G, Konovalov O et al (2005) Structural studies of the neural-cell-adhesion molecule by X-ray and neutron reflectivity. Biochemistry 44:546-554PubMedGoogle Scholar
  3. 3.
    Johnson CP, Fujimoto I, Rutishauser U et al (2005) Direct evidence that neural cell adhesion molecule (NCAM) polysialylation increases intermembrane repulsion and abrogates adhesion. J Biol Chem 280:137-145PubMedGoogle Scholar
  4. 4.
    Kleene R, Schachner M (2004) Glycans and neural cell interactions. Nat Rev Neurosci 5:195-208PubMedGoogle Scholar
  5. 5.
    Bonfanti L (2006) PSA-NCAM in mammalian structural plasticity and neurogenesis. Prog Neurobiol 80:129-164PubMedGoogle Scholar
  6. 6.
    Gascon E, Vutskits L, Kiss JZ (2007) Polysialic acid-neural cell adhesion molecule in brain plasticity: from synapses to integration of new neurons. Brain Res Rev 56:101-118PubMedGoogle Scholar
  7. 7.
    Hildebrandt H, Mühlenhoff M, Weinhold B et al (2007) Dissecting polysialic acid and NCAM functions in brain development. J Neurochem 103(Suppl 1):56-64PubMedGoogle Scholar
  8. 8.
    Rutishauser U (2008) Polysialic acid in the plasticity of the developing and adult vertebrate nervous system. Nat Rev Neurosci 9:26-35PubMedGoogle Scholar
  9. 9.
    Edelman GM, Chuong CM (1982) Embryonic to adult conversion of neural cell adhesion molecules in normal and staggerer mice. Proc Natl Acad Sci USA 79:7036-7040PubMedGoogle Scholar
  10. 10.
    Rothbard JB, Brackenbury R, Cunningham BA et al (1982) Differences in the carbohydrate structures of neural cell-adhesion molecules from adult and embryonic chicken brains. J Biol Chem 257:11064-11069PubMedGoogle Scholar
  11. 11.
    Lackie PM, Zuber C, Roth J (1991) Expression of polysialylated N-CAM during rat heart development. Differentiation 47:85-98PubMedGoogle Scholar
  12. 12.
    Lackie PM, Zuber C, Roth J (1994) Polysialic acid of the neural cell adhesion molecule (N-CAM) is widely expressed during organogenesis in mesodermal and endodermal derivatives. Differentiation 57:119-131PubMedGoogle Scholar
  13. 13.
    Probstmeier R, Bilz A, Schneider-Schaulies J (1994) Expression of the neural cell adhesion molecule and polysialic acid during early mouse embryogenesis. J Neurosci Res 37:324-335PubMedGoogle Scholar
  14. 14.
    Kurosawa N, Yoshida Y, Kojima N et al (1997) Polysialic acid synthase (ST8Sia II STX) mRNA expression in the developing mouse central nervous system. J Neurochem 69:494-503PubMedGoogle Scholar
  15. 15.
    Galuska SP, Oltmann-Norden I, Geyer H et al (2006) Polysialic acid profiles of mice expressing variant allelic combinations of the polysialyltransferases ST8SiaII and ST8SiaIV. J Biol Chem 281:31605-31615PubMedGoogle Scholar
  16. 16.
    Oltmann-Norden I, Galuska SP, Hildebrandt H et al (2008) Impact of the polysialyltransferases ST8SiaII and ST8SiaIV on polysialic acid synthesis during postnatal mouse brain development. J Biol Chem 283:1463-1471PubMedGoogle Scholar
  17. 17.
    Seki T, Arai Y (1993) Distribution and possible roles of the highly polysialylated neural cell adhesion molecule (NCAM-H) in the developing and adult central nervous system. Neurosci Res 17:265-290PubMedGoogle Scholar
  18. 18.
    Angata K, Fukuda M (2003) Polysialyltransferases: major players in polysialic acid synthesis on the neural cell adhesion molecule. Biochimie 85:195-206PubMedGoogle Scholar
  19. 19.
    Bruses JL, Rutishauser U (1998) Regulation of neural cell adhesion molecule polysialylation: evidence for nontranscriptional control and sensitivity to an intracellular pool of calcium. J Cell Biol 140:1177-1186PubMedGoogle Scholar
  20. 20.
    Gallagher HC, Odumeru OA, Regan CM (2000) Regulation of neural cell adhesion molecule polysialylation state by cell-cell contact and protein kinase C delta. J Neurosci Res 61:636-645PubMedGoogle Scholar
  21. 21.
    Gallagher HC, Murphy KJ, Foley AG et al (2001) Protein kinase C delta regulates neural cell adhesion molecule polysialylation state in the rat brain. J Neurochem 77:425-434PubMedGoogle Scholar
  22. 22.
    Kiss JZ, Wang C, Olive S et al (1994) Activity-dependent mobilization of the adhesion molecule polysialic NCAM to the cell surface of neurons and endocrine cells. EMBO J 13:5284-5292PubMedGoogle Scholar
  23. 23.
    Muller D, Wang C, Skibo G et al (1996) PSA-NCAM is required for activity-induced synaptic plasticity. Neuron 17:413-422PubMedGoogle Scholar
  24. 24.
    Roth J, Zuber C, Komminoth P, Scheidegger EP, Warhol MJ, Bitter-Suermann D, Heitz PU (1993) Expression of polysialic acid in human tumors and its significance for tumor growth. In: Roth J, Rutishauser U, Troy FA (eds) Polysialic acid. Birkhäuser Verlag, Basel, pp 335-348Google Scholar
  25. 25.
    Fukuda M (1996) Possible roles of tumor-associated carbohydrate antigens. Cancer Res 56:2237-2244PubMedGoogle Scholar
  26. 26.
    Fuster MM, Esko JD (2005) The sweet and sour of cancer: glycans as novel therapeutic targets. Nat Rev Cancer 5:526-542PubMedGoogle Scholar
  27. 27.
    Roth J, Zuber C, Wagner P et al (1988) Reexpression of poly(sialic acid) units of the neural cell adhesion molecule in Wilms tumor. Proc Natl Acad Sci USA 85:2999-3003PubMedGoogle Scholar
  28. 28.
    Figarella-Branger D, Durbec PL, Rougon GN (1990) Differential spectrum of expression of neural cell adhesion molecule isoforms and L1 adhesion molecules on human neuroectodermal tumors. Cancer Res 50:6364-6370PubMedGoogle Scholar
  29. 29.
    Komminoth P, Roth J, Lackie PM et al (1991) Polysialic acid of the neural cell adhesion molecule distinguishes small cell lung carcinoma from carcinoids. Am J Pathol 139:297-304PubMedGoogle Scholar
  30. 30.
    Kaiser U, Auerbach B, Oldenburg M (1996) The neural cell adhesion molecule NCAM in multiple myeloma. Leuk Lymphoma 20:389-395PubMedGoogle Scholar
  31. 31.
    Glüer S, Schelp C, Madry N et al (1998) Serum polysialylated neural cell adhesion molecule in childhood neuroblastoma. Br J Cancer 78:106-110PubMedGoogle Scholar
  32. 32.
    Glüer S, Schelp C, Von Schweinitz D et al (1998) Polysialylated neural cell adhesion molecule in childhood rhabdomyosarcoma. Pediatr Res 43:145-147PubMedGoogle Scholar
  33. 33.
    Hildebrandt H, Becker C, Glüer S et al (1998) Polysialic acid on the neural cell adhesion molecule correlates with expression of polysialyltransferases and promotes neuroblastoma cell growth. Cancer Res 58:779-784PubMedGoogle Scholar
  34. 34.
    Seidenfaden R, Gerardy-Schahn R, Hildebrandt H (2000) Control of NCAM polysialylation by the differential expression of polysialytransferases ST8SiaII and ST8SiaIV. Eur J Cell Biol 79:680-688PubMedGoogle Scholar
  35. 35.
    Tanaka F, Otake Y, Nakagawa T et al (2000) Expression of polysialic acid and STX, a human polysialyltransferase, is correlated with tumor progression in non-small cell lung cancer. Cancer Res 60:3072-3080PubMedGoogle Scholar
  36. 36.
    Trouillas J, Daniel L, Guigard MP et al (2003) Polysialylated neural cell adhesion molecules expressed in human pituitary tumors and related to extrasellar invasion. J Neurosurg 98:1084-1093PubMedGoogle Scholar
  37. 37.
    Scheidegger EP, Lackie PM, Papay J et al (1994) In vitro and in vivo growth of clonal sublines of human small cell lung carcinoma is modulated by polysialic acid of the neural cell adhesion molecule. Lab Invest 70:95-106PubMedGoogle Scholar
  38. 38.
    Daniel L, Trouillas J, Renaud W et al (2000) Polysialylated-neural cell adhesion molecule expression in rat pituitary transplantable tumors (spontaneous mammotropic transplantable tumor in Wistar-Furth rats) is related to growth rate and malignancy. Cancer Res 60:80-85PubMedGoogle Scholar
  39. 39.
    Daniel L, Durbec P, Gautherot E et al (2001) A nude mice model of human rhabdomyosarcoma lung metastases for evaluating the role of polysialic acids in the metastatic process. Oncogene 20:997-1004PubMedGoogle Scholar
  40. 40.
    Suzuki M, Suzuki M, Nakayama J et al (2005) Polysialic acid facilitates tumor invasion by glioma cells. Glycobiology 15:887-894PubMedGoogle Scholar
  41. 41.
    Seidenfaden R, Krauter A, Schertzinger F et al (2003) Polysialic acid directs tumor cell growth by controlling heterophilic neural cell adhesion molecule interactions. Mol Cell Biol 23:5908-5918PubMedGoogle Scholar
  42. 42.
    Seidenfaden R, Krauter A, Hildebrandt H (2006) The neural cell adhesion molecule NCAM regulates neuritogenesis by multiple mechanisms of interaction. Neurochem Int 49:1-11PubMedGoogle Scholar
  43. 43.
    Glüer S, Zense M, Radtke E et al (1998) Polysialylated neural cell adhesion molecule in childhood ganglioneuroma and neuroblastoma of different histological grade and clinical stage. Langenbecks Arch Surg 383:340-344PubMedGoogle Scholar
  44. 44.
    Cheung IY, Vickers A, Cheung NK (2006) Sialyltransferase STX (ST8SiaII): a novel molecular marker of metastatic neuroblastoma. Int J Cancer 119:152-156PubMedGoogle Scholar
  45. 45.
    Edvardsen K, Pedersen PH, Bjerkvig R et al (1994) Transfection of glioma cells with the neural-cell adhesion molecule NCAM: effect on glioma-cell invasion and growth in vivo. Int J Cancer 58:116-122PubMedGoogle Scholar
  46. 46.
    Sasaki H, Yoshida K, Ikeda E et al (1998) Expression of the neural cell adhesion molecule in astrocytic tumors: an inverse correlation with malignancy. Cancer 82:1921-1931PubMedGoogle Scholar
  47. 47.
    Perl AK, Dahl U, Wilgenbus P et al (1999) Reduced expression of neural cell adhesion molecule induces metastatic dissemination of pancreatic beta tumor cells. Nat Med 5:286-291PubMedGoogle Scholar
  48. 48.
    Eckhardt M, Mühlenhoff M, Bethe A et al (1995) Molecular characterization of eukaryotic polysialyltransferase-1. Nature 373:715-718PubMedGoogle Scholar
  49. 49.
    Nakayama J, Fukuda MN, Fredette B et al (1995) Expression cloning of a human polysialyltransferase that forms the polysialylated neural cell adhesion molecule present in embryonic brain. Proc Natl Acad Sci USA 92:7031-7035PubMedGoogle Scholar
  50. 50.
    Scheidegger EP, Sternberg LR, Roth J et al (1995) A human STX cDNA confers polysialic acid expression in mammalian cells. J Biol Chem 270:22685-22688PubMedGoogle Scholar
  51. 51.
    Kojima N, Yoshida Y, Tsuji S (1995) A developmentally regulated member of the sialyltransferase family (ST8Sia II, STX) is a polysialic acid synthase. FEBS Lett 373:119-122PubMedGoogle Scholar
  52. 52.
    Datta AK, Paulson JC (1995) The sialyltransferase “sialylmotif” participates in binding the donor substrate CMP-NeuAc. J Biol Chem 270:1497-1500PubMedGoogle Scholar
  53. 53.
    Datta AK, Sinha A, Paulson JC (1998) Mutation of the sialyltransferase S-sialylmotif alters the kinetics of the donor and acceptor substrates. J Biol Chem 273:9608-9614PubMedGoogle Scholar
  54. 54.
    Inoue S, Lin SL, Inoue Y (2000) Chemical analysis of the developmental pattern of polysialylation in chicken brain expression of only an extended form of polysialyl chains during embryogenesis and the presence of disialyl residues in both embryonic and adult chicken brains. J Biol Chem 275:29968-29979PubMedGoogle Scholar
  55. 55.
    Nakata D, Troy FA (2005) Degree of polymerization (DP) of polysialic acid (polySia) on neural cell adhesion molecules (N-CAMS): development and application of a new strategy to accurately determine the DP of polySia chains on N-CAMS. J Biol Chem 280:38305-38316PubMedGoogle Scholar
  56. 56.
    Galuska SP, Geyer R, Gerardy-Schahn R et al (2008) Enzyme-dependent variations in the polysialylation of the neural cell adhesion molecule (NCAM) in vivo. J Biol Chem 283:17-28PubMedGoogle Scholar
  57. 57.
    Zuber C, Lackie PM, Catterall WA et al (1992) Polysialic acid is associated with sodium channels and the neural cell adhesion molecule N-CAM in adult rat brain. J Biol Chem 267:9965-9971PubMedGoogle Scholar
  58. 58.
    Yabe U, Sato C, Matsuda T et al (2003) Polysialic acid in human milk. CD36 is a new member of mammalian polysialic acid-containing glycoprotein. J Biol Chem 278:13875-13880PubMedGoogle Scholar
  59. 59.
    Curreli S, Arany Z, Gerardy-Schahn R et al (2007) Polysialylated neuropilin-2 is expressed on the surface of human dendritic cells and modulates dendritic cell-T lymphocyte interactions. J Biol Chem 282:30346-30356PubMedGoogle Scholar
  60. 60.
    Mühlenhoff M, Eckhardt M, Bethe A et al (1996) Autocatalytic polysialylation of polysialyltransferase-1. EMBO J 15:6943-6950PubMedGoogle Scholar
  61. 61.
    Close BE, Colley KJ (1998) In vivo autopolysialylation and localization of the polysialyltransferases PST and STX. J Biol Chem 273:34586-34593PubMedGoogle Scholar
  62. 62.
    Close BE, Tao K, Colley KJ (2000) Polysialyltransferase-1 autopolysialylation is not requisite for polysialylation of neural cell adhesion molecule. J Biol Chem 275:4484-4491PubMedGoogle Scholar
  63. 63.
    Weinhold B, Seidenfaden R, Röckle I et al (2005) Genetic ablation of polysialic acid causes severe neurodevelopmental defects rescued by deletion of the neural cell adhesion molecule. J Biol Chem 280:42971-42977PubMedGoogle Scholar
  64. 64.
    Mühlenhoff M, Eckhardt M, Bethe A et al (1996) Polysialylation of NCAM by a single enzyme. Curr Biol 6:1188-1191PubMedGoogle Scholar
  65. 65.
    Angata K, Suzuki M, Fukuda M (1998) Differential and cooperative polysialylation of the neural cell adhesion molecule by two polysialyltransferases, PST and STX. J Biol Chem 273:28524-28532PubMedGoogle Scholar
  66. 66.
    Nelson RW, Bates PA, Rutishauser U (1995) Protein determinants for specific polysialylation of the neural cell adhesion molecule. J Biol Chem 270:17171-17179PubMedGoogle Scholar
  67. 67.
    Liedtke S, Geyer H, Wuhrer M et al (2001) Characterization of N-glycans from mouse brain neural cell adhesion molecule. Glycobiology 11:373-384PubMedGoogle Scholar
  68. 68.
    von der Ohe M, Wheeler SF, Wuhrer M et al (2002) Localization and characterization of polysialic acid-containing N-linked glycans from bovine NCAM. Glycobiology 12:47-63Google Scholar
  69. 69.
    Kudo M, Kitajima K, Inoue S et al (1996) Characterization of the major core structures of the alpha2->8- linked polysialic acid-containing glycan chains present in neural cell adhesion molecule in embryonic chick brains. J Biol Chem 271:32667-32677PubMedGoogle Scholar
  70. 70.
    Geyer H, Bahr U, Liedtke S et al (2001) Core structures of polysialylated glycans present in neural cell adhesion molecule from newborn mouse brain. Eur J Biochem 268:6587-6599PubMedGoogle Scholar
  71. 71.
    Wuhrer M, Geyer H, von der Ohe M et al (2003) Localization of defined carbohydrate epitopes in bovine polysialylated NCAM. Biochimie 85:207-218PubMedGoogle Scholar
  72. 72.
    Mendiratta SS, Sekulic N, Hernandez-Guzman FG et al (2006) A novel alpha-helix in the first fibronectin type III repeat of the neural cell adhesion molecule is critical for N-glycan polysialylation. J Biol Chem 281:36052-36059PubMedGoogle Scholar
  73. 73.
    Kojima N, Tachida Y, Yoshida Y et al (1996) Characterization of mouse ST8Sia II (STX) as a neural cell adhesion molecule-specific polysialic acid synthase - requirement of core alpha-1, 6-linked fucose and a polypeptide chain for polysialylation. J Biol Chem 271:19457-19463PubMedGoogle Scholar
  74. 74.
    Angata K, Suzuki M, McAuliffe J et al (2000) Differential Biosynthesis of Polysialic Acid on NCAM and Oligosaccharide Acceptors by Three Distinct a2, 8-Sialyltransferases, ST8Sia IV (PST), ST8Sia II (STX), and ST8Sia III. J Biol Chem 275:18594-18601PubMedGoogle Scholar
  75. 75.
    Angata K, Suzuki M, Fukuda M (2002) ST8Sia II and ST8Sia IV polysialyltransferases exhibit marked differences in utilizing various acceptors containing oligosialic acid and short polysialic acid. The basis for cooperative polysialylation by two enzymes. J Biol Chem 277:36808-36817PubMedGoogle Scholar
  76. 76.
    Kitazume-Kawaguchi S, Kabata S, Arita M (2001) Differential Biosynthesis of Polysialic or Disialic Acid Structure by ST8Sia II and ST8Sia IV. J Biol Chem 276:15696-15703PubMedGoogle Scholar
  77. 77.
    Eckhardt M, Bukalo O, Chazal G et al (2000) Mice deficient in the polysialyltransferase ST8SiaIV/PST-1 allow discrimination of the roles of neural cell adhesion molecule protein and polysialic acid in neural development and synaptic plasticity. J Neurosci 20:5234-5244PubMedGoogle Scholar
  78. 78.
    Angata K, Long JM, Bukalo O et al (2004) Sialyltransferase ST8Sia-II assembles a subset of polysialic acid that directs hippocampal axonal targeting and promotes fear behavior. J Biol Chem 279:32603-32613PubMedGoogle Scholar
  79. 79.
    Angata K, Nakayama J, Fredette B et al (1997) Human STX polysialyltransferase forms the embryonic form of the neural cell adhesion molecule - tissue-specific expression, neurite outgrowth, and chromosomal localization in comparison with another polysialyltransferase PST. J Biol Chem 272:7182-7190PubMedGoogle Scholar
  80. 80.
    Phillips GR, Krushel LA, Crossin KL (1997) Developmental expression of two rat sialyltransferases that modify the neural cell adhesion molecule N-CAM. Dev Brain Res 102:143-155Google Scholar
  81. 81.
    Hildebrandt H, Becker C, Mürau M et al (1998) Heterogeneous expression of the polysialyltransferases ST8Sia II and ST8Sia IV during postnatal rat brain development. J Neurochem 71:2339-2348PubMedGoogle Scholar
  82. 82.
    Ong E, Nakayama J, Angata K et al (1998) Developmental regulation of polysialic acid synthesis in mouse directed by two polysialyltransferases, PST and STX. Glycobiology 8:415-424PubMedGoogle Scholar
  83. 83.
    Yoshida Y, Kurosawa N, Kanematsu T et al (1996) Genomic structure and promoter activity of the mouse polysialic acid synthase gene (mST8Sia II) - brain-specific expression from a tata-less gc-rich sequence. J Biol Chem 271:30167-30173PubMedGoogle Scholar
  84. 84.
    Eckhardt M, Gerardy-Schahn R (1998) Genomic organization of the murine polysialyltransferase gene ST8SiaIV (PST-1). Glycobiology 8:1165-1172PubMedGoogle Scholar
  85.  85.
    Takashima S, Yoshida Y, Kanematsu T et al (1998) Genomic structure and promoter activity of the mouse polysialic acid synthase (mST8Sia IV/PST) gene. J Biol Chem 273:7675-7683PubMedGoogle Scholar
  86.  86.
    Seidenfaden R, Hildebrandt H (2001) Retinoic acid-induced changes in NCAM polysialylation and polysialyltransferase mRNA expression of human neuroblastoma cells. J Neurobiol 46:11-28PubMedGoogle Scholar
  87. 87.
    Beecken WD, Engl T, Ogbomo H et al (2005) Valproic acid modulates NCAM polysialylation and polysialyltransferase mRNA expression in human tumor cells. Int Immunopharmacol 5:757-769PubMedGoogle Scholar
  88. 88.
    Mayanil CS, George D, Mania-Farnell B et al (2000) Overexpression of murine Pax3 increases NCAM polysialylation in a human medulloblastoma cell line. J Biol Chem 275(30):23259-23266PubMedGoogle Scholar
  89. 89.
    Marx M, Rivera-Milla E, Stummeyer K et al (2007) Divergent evolution of the vertebrate polysialyltransferase Stx and Pst genes revealed by fish-to-mammal comparison. Dev Biol 306:560-571PubMedGoogle Scholar
  90. 90.
    Rieger S, Volkmann K, Koster RW (2008) Polysialyltransferase expression is linked to neuronal migration in the developing and adult zebrafish. Dev Dyn 237:276-285PubMedGoogle Scholar
  91. 91.
    Vaithianathan T, Matthias K, Bahr B et al (2004) Neural cell adhesion molecule-associated polysialic acid potentiates alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor currents. J Biol Chem 279:47975-47984PubMedGoogle Scholar
  92.  92.
    Hammond MS, Sims C, Parameshwaran K et al (2006) NCAM associated polysialic acid inhibits NR2B-containing NMDA receptors and prevents glutamate-induced cell death. J Biol Chem 281:34859-34869PubMedGoogle Scholar
  93.  93.
    Senkov O, Sun M, Weinhold B et al (2006) Polysialylated neural cell adhesion molecule is involved in induction of long-term potentiation and memory acquisition and consolidation in a fear-conditioning paradigm. J Neurosci 26:10888-10898PubMedGoogle Scholar
  94.  94.
    Stoenica L, Senkov O, Gerardy-Schahn R et al (2006) In vivo synaptic plasticity in the dentate gyrus of mice deficient in the neural cell adhesion molecule NCAM or its polysialic acid. Eur J NeuroSci 23:2255-2264PubMedGoogle Scholar
  95.  95.
    Cremer H, Lange R, Christoph A et al (1994) Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning. Nature 367:455-459PubMedGoogle Scholar
  96.  96.
    Tomasiewicz H, Ono K, Yee D et al (1993) Genetic deletion of a neural cell adhesion molecule variant (N- CAM-180) produces distinct defects in the central nervous system. Neuron 11:1163-1174PubMedGoogle Scholar
  97. 97.
    Ono K, Tomasiewicz H, Magnuson T et al (1994) N-CAM mutation inhibits tangential neuronal migration and is phenocopied by enzymatic removal of polysialic acid. Neuron 13:595-609PubMedGoogle Scholar
  98.  98.
    Hu H, Tomasiewicz H, Magnuson T et al (1996) The role of polysialic acid in migration of olfactory bulb interneuron precursors in the subventricular zone. Neuron 16:735-743PubMedGoogle Scholar
  99. 99.
    Chazal G, Durbec P, Jankovski A et al (2000) Consequences of neural cell adhesion molecule deficiency on cell migration in the rostral migratory stream of the mouse. J Neurosci 20:1446-1457PubMedGoogle Scholar
  100. 100.
    Cremer H, Chazal G, Goridis C et al (1997) NCAM is essential for axonal growth and fasciculation in the hippocampus. Mol Cell Neurosci 8:323-335PubMedGoogle Scholar
  101. 101.
    Seki T, Rutishauser U (1998) Removal of polysialic acid-neural cell adhesion molecule induces aberrant mossy fiber innervation and ectopic synaptogenesis in the hippocampus. J Neurosci 18:3757-3766PubMedGoogle Scholar
  102. 102.
    Angata K, Huckaby V, Ranscht B et al (2007) Polysialic acid-directed migration and differentiation of neural precursors is essential for mouse brain development. Mol Cell Biol 27:6659-6668PubMedGoogle Scholar
  103. 103.
    Gravvanis AI, Lavdas A, Papalois AE et al (2005) Effect of genetically modified Schwann cells with increased motility in end-to-side nerve grafting. Microsurgery 25:423-432PubMedGoogle Scholar
  104. 104.
    El Maarouf A, Petridis AK, Rutishauser U (2006) Use of polysialic acid in repair of the central nervous system. Proc Natl Acad Sci USA 103:16989-16994PubMedGoogle Scholar
  105. 105.
    Lavdas AA, Franceschini I, Dubois-Dalcq M et al (2006) Schwann cells genetically engineered to express PSA show enhanced migratory potential without impairment of their myelinating ability in vitro. Glia 53:868-878PubMedGoogle Scholar
  106. 106.
    Papastefanaki F, Chen J, Lavdas AA et al (2007) Grafts of Schwann cells engineered to express PSA-NCAM promote functional recovery after spinal cord injury. Brain 130:2159-2174PubMedGoogle Scholar
  107. 107.
    Glaser T, Brose C, Franceschini I et al (2007) Neural cell adhesion molecule polysialylation enhances the sensitivity of embryonic stem cell-derived neural precursors to migration guidance cues. Stem Cells 25:3016-3025PubMedGoogle Scholar
  108. 108.
    Zhang Y, Ghadiri-Sani M, Zhang X et al (2007) Induced expression of polysialic acid in the spinal cord promotes regeneration of sensory axons. Mol Cell Neurosci 35:109-119PubMedGoogle Scholar
  109. 109.
    Zhang Y, Zhang X, Wu D et al (2007) Lentiviral-mediated expression of polysialic acid in spinal cord and conditioning lesion promote regeneration of sensory axons into spinal cord. Mol Ther 15:1796-1804PubMedGoogle Scholar
  110. 110.
    Zhang Y, Zhang X, Yeh J et al (2007) Engineered expression of polysialic acid enhances Purkinje cell axonal regeneration in L1/GAP-43 double transgenic mice. Eur J NeuroSci 25:351-361PubMedGoogle Scholar
  111. 111.
    Haile Y, Haastert K, Cesnulevicius K et al (2007) Culturing of glial and neuronal cells on polysialic acid. Biomaterials 28:1163-1173PubMedGoogle Scholar
  112. 112.
    Bruns S, Stark Y, Roker S et al (2007) Collagen biomaterial doped with colominic acid for cell culture applications with regard to peripheral nerve repair. J Biotechnol 131:335-345PubMedGoogle Scholar
  113. 113.
    Haile Y, Berski S, Dräger G et al (2008) The effect of modified polysialic acid based hydrogels on the adhesion and viability of primary neurons and glial cells. Biomaterials 29:1880-1891PubMedGoogle Scholar
  114. 114.
    Stark Y, Bruns S, Stahl F et al (2008) A study on polysialic acid as a biomaterial for cell culture applications. J Biomed Mater Res A 85:1-13PubMedGoogle Scholar
  115. 115.
    Stummeyer K, Dickmanns A, Mühlenhoff M et al (2005) Crystal structure of the polysialic acid-degrading endosialidase of bacteriophage K1F. Nat Struct Mol Biol 12:90-96PubMedGoogle Scholar
  116. 116.
    Jakobsson E, Jokilammi A, Aalto J et al (2007) Identification of amino acid residues at the active site of endosialidase that dissociate the polysialic acid binding and cleaving activities in Escherichia coli K1 bacteriophages. Biochem J 405:465-472PubMedGoogle Scholar
  117. 117.
    Schwarzer D, Stummeyer K, Gerardy-Schahn R et al (2007) Characterization of a novel intramolecular chaperone domain conserved in endosialidases and other bacteriophage tail spike and fiber proteins. J Biol Chem 282:2821-2831PubMedGoogle Scholar
  118. 118.
    Berezin V, Bock E (2004) NCAM mimetic peptides: pharmacological and therapeutic potential. J Mol Neurosci 22:33-39PubMedGoogle Scholar
  119. 119.
    Torregrossa P, Buhl L, Bancila M et al (2004) Selection of poly-alpha 2, 8-sialic acid mimotopes from a random phage peptide library and analysis of their bioactivity. J Biol Chem 279:30707-30714PubMedGoogle Scholar
  120. 120.
    Florian C, Foltz J, Norreel JC et al (2006) Post-training intrahippocampal injection of synthetic poly-alpha-2, 8-sialic acid-neural cell adhesion molecule mimetic peptide improves spatial long-term performance in mice. Learn Mem 13:335-341PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Herbert Hildebrandt
  • Martina Mühlenhoff
  • Rita Gerardy-Schahn
    • 1
    Email author
  1. 1.Institute of Cellular ChemistryHannover Medical SchoolHannoverGermany

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