Skip to main content
SpringerLink
Log in

Soluble NCAM

  • Chapter
  • First Online:
Structure and Function of the Neural Cell Adhesion Molecule NCAM

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 663))

Abstract

The neural cell adhesion molecule (NCAM) is a membrane-bound glycoprotein involved in homophilic interactions that facilitate cell-cell adhesion. In addition to a number of membrane-bound isoforms, NCAM also exists in several soluble isoforms that have been identified in cerebrospinal fluid, blood serum, brain tissue, and cell culture media. Soluble NCAM can be produced in a number of ways, such as alternative splicing of the transcript from NCAM1 and enzymatic processing of the extracellular domain at the cell membrane. Soluble NCAM interferes with homophilic NCAM interactions mediated by membrane-bound NCAM, thereby reducing NCAM-dependent adhesion, and can modulate neurite outgrowth in vitro - a property that likely is dose dependent. The biological effects of overexpressing soluble NCAM in transgenic animals include a perturbation of synaptic connectivity and the development of abnormal behaviors. Similarly, the levels of soluble NCAM in cerebrospinal fluid and blood serum are altered in many human neurological disorders.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Berezin V, Bock E, Poulsen F (2000) The neural cell adhesion molecule NCAM. Curr Opin Drug Discov Devel 3:605-609

    PubMed  CAS  Google Scholar 

  2. Hinsby AM, Berezin V, Bock E (2004) Molecular mechanisms of NCAM function. Front Biosci 9:2227-2244

    Article  PubMed  CAS  Google Scholar 

  3. Cunningham BA, Hemperly JJ, Murray BA et al (1987) Neural cell adhesion molecule: structure, immunoglobulin-like domains, cell surface modulation, and alternative RNA splicing. Science 236:799-806

    Article  PubMed  CAS  Google Scholar 

  4. Colwell G, Li B, Forrest D et al (1992) Conserved regulatory elements in the promoter region of the N-CAM gene. Genomics 14:875-882

    Article  PubMed  CAS  Google Scholar 

  5. Owens GC, Edelman GM, Cunningham BA (1987) Organization of the neural cell adhesion molecule (N-CAM) gene: alternative exon usage as the basis for different membrane-associated domains. Proc Natl Acad Sci U S A 84:294-298

    Article  PubMed  CAS  Google Scholar 

  6. He HT, Barbet J, Chaix JC et al (1986) Phosphatidylinositol is involved in the membrane attachment of NCAM-120, the smallest component of the neural cell adhesion molecule. EMBO J 5:2489-2494

    PubMed  CAS  Google Scholar 

  7. Small SJ, Akeson R (1990) Expression of the unique NCAM VASE exon is independently regulated in distinct tissues during development. J Cell Biol 111:2089-2096

    Article  PubMed  CAS  Google Scholar 

  8. Liedtke S, Geyer H, Wuhrer M et al (2001) Characterization of N-glycans from mouse brain neural cell adhesion molecule. Glycobiology 11:373-384

    Article  PubMed  CAS  Google Scholar 

  9. Ibsen S, Berezin V, Norgaard-Pedersen B et al (1983) Quantification of the D2-glycoprotein in amniotic fluid and serum from pregnancies with fetal neural tube defects. J Neurochem 41:363-366

    Article  PubMed  CAS  Google Scholar 

  10. Jorgensen OS, Bock E (1975) Synaptic plasma membrane antigen D2 measured in human cerebrospinal fluid by rocket-line immunoelectrophoresis. Determination in psychiatric and neurological patients. Scand J Immunol 4(Suppl 2):25-30

    Google Scholar 

  11. Nybroe O, Linnemann D, Bock E (1989) Heterogeneity of soluble neural cell adhesion molecule. J Neurochem 53:1372-1378

    Article  PubMed  CAS  Google Scholar 

  12. Rutishauser U, Thiery JP, Brackenbury R et al (1976) Mechanisms of adhesion among cells from neural tissues of the chick embryo. Proc Natl Acad Sci U S A 73:577-581

    Article  PubMed  CAS  Google Scholar 

  13. Krog L, Olsen M, Dalseg AM et al (1992) Characterization of soluble neural cell adhesion molecule in rat brain, CSF, and plasma. J Neurochem 59:838-847

    Article  PubMed  CAS  Google Scholar 

  14. Olsen M, Krog L, Edvardsen K et al (1993) Intact transmembrane isoforms of the neural cell adhesion molecule are released from the plasma membrane. Biochem J 295:833-840

    PubMed  CAS  Google Scholar 

  15. Dalseg AM, Linnemann D, Bock E (1989) Soluble neural cell adhesion molecule in brain, cerebrospinal fluid and plasma in the developing rat. Int J Dev Neurosci 7:209-217

    Article  PubMed  CAS  Google Scholar 

  16. Bock E, Edvardsen K, Gibson A et al (1987) Characterization of soluble forms of NCAM. FEBS Lett 225:33-36

    Article  PubMed  CAS  Google Scholar 

  17. Todaro L, Puricelli L, Gioseffi H et al (2004) Neural cell adhesion molecule in human serum. Increased levels in dementia of the Alzheimer type. Neurobiol Dis 15:387-393

    Article  PubMed  CAS  Google Scholar 

  18. Poltorak M, Frye MA, Wright R et al (1996) Increased neural cell adhesion molecule in the CSF of patients with mood disorder. J Neurochem 66:1532-1538

    Article  PubMed  CAS  Google Scholar 

  19. Poltorak M, Khoja I, Hemperly JJ et al (1995) Disturbances in cell recognition molecules (N-CAM and L1 antigen) in the CSF of patients with schizophrenia. Exp Neurol 131:266-272

    Article  PubMed  CAS  Google Scholar 

  20. Poltorak M, Wright R, Hemperly JJ et al (1997) Monozygotic twins discordant for schizophrenia are discordant for N-CAM and L1 in CSF. Brain Res 751:152-154

    Article  PubMed  CAS  Google Scholar 

  21. van Kammen DP, Poltorak M, Kelley ME et al (1998) Further studies of elevated cerebrospinal fluid neuronal cell adhesion molecule in schizophrenia. Biol Psychiatry 43:680-686

    Article  PubMed  Google Scholar 

  22. Strekalova H, Buhmann C, Kleene R et al (2006) Elevated levels of neural recognition molecule L1 in the cerebrospinal fluid of patients with Alzheimer disease and other dementia syndromes. Neurobiol Aging 27:1-9

    Article  PubMed  CAS  Google Scholar 

  23. Takamatsu K, Auerbach B, Gerardy-Schahn R et al (1994) Characterization of tumor-associated neural cell adhesion molecule in human serum. Cancer Res 54:2598-2603

    PubMed  CAS  Google Scholar 

  24. Weisgerber C, Husmann M, Frosch M et al (1990) Embryonic neural cell adhesion molecule in cerebrospinal fluid of younger children: age-dependent decrease during the first year. J Neurochem 55:2063-2071

    Article  PubMed  CAS  Google Scholar 

  25. Vawter MP, Usen N, Thatcher L et al (2001) Characterization of human cleaved N-CAM and association with schizophrenia. Exp Neurol 172:29-46

    Article  PubMed  CAS  Google Scholar 

  26. Lyles JM, Linnemann D, Bock E (1984) Biosynthesis of the D2-cell adhesion molecule: post-translational modifications, intracellular transport, and developmental changes. J Cell Biol 99:2082-2091

    Article  PubMed  CAS  Google Scholar 

  27. Gower HJ, Barton CH, Elsom VL et al (1988) Alternative splicing generates a secreted form of N-CAM in muscle and brain. Cell 55:955-964

    Article  PubMed  CAS  Google Scholar 

  28. Sadoul K, Meyer A, Low MG et al (1986) Release of the 120 kDa component of the mouse neural cell adhesion molecule N-CAM from cell surfaces by phosphatidylinositol-specific phospholipase C. Neurosci Lett 72:341-346

    Article  PubMed  CAS  Google Scholar 

  29. Diestel S, Hinkle CL, Schmitz B et al (2005) NCAM140 stimulates integrin-dependent cell migration by ectodomain shedding. J Neurochem 95:1777-1784

    Article  PubMed  CAS  Google Scholar 

  30. Hinkle CL, Diestel S, Lieberman J et al (2006) Metalloprotease-induced ectodomain shedding of neural cell adhesion molecule (NCAM). J Neurobiol 66:1378-1395

    Article  PubMed  CAS  Google Scholar 

  31. Hubschmann MV, Skladchikova G, Bock E et al (2005) Neural cell adhesion molecule function is regulated by metalloproteinase-mediated ectodomain release. J Neurosci Res 80:826-837

    Article  PubMed  Google Scholar 

  32. Kalus I, Bormann U, Mzoughi M et al (2006) Proteolytic cleavage of the neural cell adhesion molecule by ADAM17/TACE is involved in neurite outgrowth. J Neurochem 98:78-88

    Article  PubMed  CAS  Google Scholar 

  33. Probstmeier R, Kuhn K, Schachner M (1989) Binding properties of the neural cell adhesion molecule to different components of the extracellular matrix. J Neurochem 53:1794-1801

    Article  PubMed  CAS  Google Scholar 

  34. Probstmeier R, Fahrig T, Spiess E et al (1992) Interactions of the neural cell adhesion molecule and the myelin-associated glycoprotein with collagen type I: involvement in fibrillogenesis. J Cell Biol 116:1063-1070

    Article  PubMed  CAS  Google Scholar 

  35. Soroka V, Kiryushko D, Novitskaya V et al (2002) Induction of neuronal differentiation by a peptide corresponding to the homophilic binding site of the second Ig module of the neural cell adhesion molecule. J Biol Chem 277:24676-24683

    Article  PubMed  CAS  Google Scholar 

  36. Thomaidou D, Coquillat D, Meintanis S et al (2001) Soluble forms of NCAM and F3 neuronal cell adhesion molecules promote Schwann cell migration: identification of protein tyrosine phosphatases ζ/β as the putative F3 receptors on Schwann cells. J Neurochem 78:767-778

    Article  PubMed  CAS  Google Scholar 

  37. Pillai-Nair N, Panicker AK, Rodriguiz RM et al (2005) Neural cell adhesion molecule-secreting transgenic mice display abnormalities in GABAergic interneurons and alterations in behavior. J Neurosci 25:4659-4671

    Article  PubMed  CAS  Google Scholar 

  38. DiMilla PA, Barbee K, Lauffenburger DA (1991) Mathematical model for the effects of adhesion and mechanics on cell migration speed. Biophys J 60:15-37

    Article  PubMed  CAS  Google Scholar 

  39. Palecek SP, Loftus JC, Ginsberg MH et al (1997) Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness. Nature 385:537-540

    Article  PubMed  CAS  Google Scholar 

  40. Karkkainen I, Rybnikova E, Pelto-Huikko M et al (2000) Metalloprotease-disintegrin (ADAM) genes are widely and differentially expressed in the adult CNS. Mol Cell Neurosci 15:547-560

    Article  PubMed  CAS  Google Scholar 

  41. Rabinowitz JE, Rutishauser U, Magnuson T (1996) Targeted mutation of Ncam to produce a secreted molecule results in a dominant embryonic lethality. Proc Natl Acad Sci U S A 93:6421-6424

    Article  PubMed  CAS  Google Scholar 

  42. 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 367:455-459

    Article  PubMed  CAS  Google Scholar 

  43. 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 11:1163-1174

    Article  PubMed  CAS  Google Scholar 

  44. Treloar H, Tomasiewicz H, Magnuson T et al (1997) The central pathway of primary olfactory axons is abnormal in mice lacking the N-CAM-180 isoform. J Neurobiol 32:643-658

    Article  PubMed  CAS  Google Scholar 

  45. Stork O, Welzl H, Wolfer D et al (2000) Recovery of emotional behaviour in neural cell adhesion molecule (NCAM) null mutant mice through transgenic expression of NCAM180. Eur J NeuroSci 12:3291-3306

    Article  PubMed  CAS  Google Scholar 

  46. Wood GK, Tomasiewicz H, Rutishauser U et al (1998) NCAM-180 knockout mice display increased lateral ventricle size and reduced prepulse inhibition of startle. NeuroReport 9:461-466

    Article  PubMed  CAS  Google Scholar 

  47. Stork O, Welzl H, Cremer H et al (1997) Increased intermale aggression and neuroendocrine response in mice deficient for the neural cell adhesion molecule (NCAM). Eur J NeuroSci 9:1117-1125

    Article  PubMed  CAS  Google Scholar 

  48. Stork O, Welzl H, Wotjak CT et al (1999) Anxiety and increased 5-HT1A receptor response in NCAM null mutant mice. J Neurobiol 40:343-355

    Article  PubMed  CAS  Google Scholar 

  49. Forss-Petter S, Danielson PE, Catsicas S et al (1990) Transgenic mice expressing β-galactosidase in mature neurons under neuron-specific enolase promoter control. Neuron 5:187-197

    Article  PubMed  CAS  Google Scholar 

  50. Lipska BK, Weinberger DR (2000) To model a psychiatric disorder in animals: schizophrenia as a reality test. Neuropsychopharmacology 23:223-239

    Article  PubMed  CAS  Google Scholar 

  51. Lyons F, Martin ML, Maguire C et al (1988) The expression of an N-CAM serum fragment is positively correlated with severity of negative features in type II schizophrenia. Biol Psychiatry 23:769-775

    Article  PubMed  CAS  Google Scholar 

  52. Jorgensen OS (1988) Neural cell adhesion molecule (NCAM) and prealbumin in cerebrospinal fluid from depressed patients. Acta Psychiatr Scand Suppl 345:29-37

    PubMed  CAS  Google Scholar 

  53. Vawter MP, Cannon-Spoor HE, Hemperly JJ et al (1998) Abnormal expression of cell recognition molecules in schizophrenia. Exp Neurol 149:424-432

    Article  PubMed  CAS  Google Scholar 

  54. Vawter MP, Frye MA, Hemperly JJ et al (2000) Elevated concentration of N-CAM VASE isoforms in schizophrenia. J Psychiatr Res 34:25-34

    Article  PubMed  CAS  Google Scholar 

  55. Vawter MP, Hemperly JJ, Freed WJ et al (1998) CSF N-CAM in neuroleptic-naive first-episode patients with schizophrenia. Schizophr Res 34:123-131

    Article  PubMed  CAS  Google Scholar 

  56. Jorgensen OS, Bock E, Bech P et al (1977) Synaptic membrane protein D2 in the cerebrospinal fluid of manic-melancholic patients. Acta Psychiatr Scand 56:50-56

    Article  PubMed  CAS  Google Scholar 

  57. Vawter MP, Hemperly JJ, Hyde TM et al (1998) VASE-containing N-CAM isoforms are increased in the hippocampus in bipolar disorder but not schizophrenia. Exp Neurol 154:1-11

    Article  PubMed  CAS  Google Scholar 

  58. Vawter MP, Howard AL, Hyde TM et al (1999) Alterations of hippocampal secreted N-CAM in bipolar disorder and synaptophysin in schizophrenia. Mol Psychiatry 4:467-475

    Article  PubMed  CAS  Google Scholar 

  59. Sorensen PS, Gjerris F, Ibsen S et al (1983) Low cerebrospinal fluid concentration of brain-specific protein D2 in patients with normal pressure hydrocephalus. J Neurol Sci 62:59-65

    Article  PubMed  CAS  Google Scholar 

  60. Massaro AR, Albrechtsen M, Bock E (1987) N-CAM in cerebrospinal fluid: a marker of synaptic remodelling after acute phases of multiple sclerosis? Ital J Neurol Sci 6:85-88

    PubMed  Google Scholar 

  61. Werdelin L, Gjerris A, Boysen G et al (1989) Neuropeptides and neural cell adhesion molecule (NCAM) in CSF from patients with ALS. Acta Neurol Scand 79:177-181

    Article  PubMed  CAS  Google Scholar 

  62. Jin L, Hemperly JJ, Lloyd RV (1991) Expression of neural cell adhesion molecule in normal and neoplastic human neuroendocrine tissues. Am J Pathol 138:961-969

    PubMed  CAS  Google Scholar 

  63. Molenaar WM, de Leij L, Trojanowski JQ (1991) Neuroectodermal tumors of the peripheral and the central nervous system share neuroendocrine N-CAM-related antigens with small cell lung carcinomas. Acta Neuropathol 83:46-54

    Article  PubMed  CAS  Google Scholar 

  64. Lantuejoul S, Moro D, Michalides RJ et al (1998) Neural cell adhesion molecules (NCAM) and NCAM-PSA expression in neuroendocrine lung tumors. Am J Surg Pathol 22:1267-1276

    Article  PubMed  CAS  Google Scholar 

  65. Vangsted A, Drivsholm L, Andersen E et al (1994) New serum markers for small-cell lung cancer. II. The neural cell adhesion molecule, NCAM. Cancer Detect Prev 18:291-298

    PubMed  CAS  Google Scholar 

  66. Ledermann JA, Pasini F, Olabiran Y et al (1994) Detection of the neural cell adhesion molecule (NCAM) in serum of patients with small-cell lung cancer (SCLC) with “limited” or “extensive” disease, and bone-marrow infiltration. Int J Cancer Suppl 8:49-52

    Article  PubMed  CAS  Google Scholar 

  67. Jaques G, Auerbach B, Pritsch M et al (1993) Evaluation of serum neural cell adhesion molecule as a new tumor marker in small cell lung cancer. Cancer 72:418-425

    Article  PubMed  CAS  Google Scholar 

  68. Lynch DF Jr, Hassen W, Clements MA et al (1997) Serum levels of endothelial and neural cell adhesion molecules in prostate cancer. Prostate 32:214-220

    Article  PubMed  CAS  Google Scholar 

  69. Figarella-Branger D, Dubois C, Chauvin P et al (1996) Correlation between polysialic-neural cell adhesion molecule levels in CSF and medulloblastoma outcomes. J Clin Oncol 14:2066-2072

    PubMed  CAS  Google Scholar 

  70. Jorgensen OS, Hemmingsen R, Kramp P et al (1980) Blood-brain barrier selectivity and synaptic turnover during delirium tremens and related clinical states. A study of brain and blood proteins in the cerebrospinal fluid. Acta Psychiatr Scand 61:356-364

    Article  PubMed  CAS  Google Scholar 

  71. Jorgensen OS, Norgaard-Pedersen B (1981) The synaptic membrane D2-protein in amniotic fluid from pregnancies with fetal neural tube defects. Prenat Diagn 1:3-6

    Article  PubMed  CAS  Google Scholar 

  72. Jorgensen OS (1982) Fetal neural tube defects detected by rocket-on-line immunoelectrophoresis of amniotic fluids. Clin Chim Acta 124:179-186

    Article  PubMed  CAS  Google Scholar 

  73. Plioplys AV, Hemmens SE, Regan CM (1990) Expression of a neural cell adhesion molecule serum fragment is depressed in autism. J Neuropsychiatry Clin Neurosci 2:413-417

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Protein Laboratory, Panum Institute, University of Copenhagen, Building 24.2, Blegdamsvej 3C, Copenhagen, DK-2200, Denmark

    Thomas Secher

Authors
  1. Thomas Secher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Secher .

Editor information

Editors and Affiliations

  1. Panum Institute, Dept. Regenerative Medicine, University of Copenhagen, Blegdamsvej 3C, Koebenhavn N, 2200, Denmark

    Vladimir Berezin

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Secher, T. (2010). Soluble NCAM. In: Berezin, V. (eds) Structure and Function of the Neural Cell Adhesion Molecule NCAM. Advances in Experimental Medicine and Biology, vol 663. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1170-4_15

Download citation

Publish with us

Policies and ethics

Search

Navigation