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Structural Biology of NCAM

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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) mediates Ca2+-independent cell-cell and cell-substratum adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM molecules) binding. NCAM is highly expressed in the nervous system and plays a key role in neural development, regeneration and synaptic plasticity, including learning and memory consolidation. The questions in the structural biology of NCAM are mainly focused on the mechanism of cell-cell interactions and the regulation of the molecular interactions involved. Numerous attempts to elucidate the homophilic binding mechanism of NCAM have produced several seemingly contradicting models. In this review, we will detail the progress made to date in the field.

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References

  1. Wilson HV (1907) On some phenomena of coalescence and regeneration in sponges. J Exp Zool 5:245-258

    Article  Google Scholar 

  2. Townes PL, Holtfreter J (1955) Directed movements and selective adhesion of embryonic amphibian cells. J Exp Zool 128:53-120

    Article  Google Scholar 

  3. Walmod PS, Pedersen MV, Berezin V, Bock E (2007) Cell adhesion molecules of the immunoglobulin superfamily in the nervous system. In: Lajtha A, Banik N (eds) Handbook of neurochemistry and molecular neurobiology, vol 7, Neural protein metabolism and function. Springer, New York, pp 35-152

    Chapter  Google Scholar 

  4. Williams AF, Barclay AN (1988) The immunoglobulin superfamily-domains for cell surface recognition. Annu Rev Immunol 6:381-405

    Article  PubMed  CAS  Google Scholar 

  5. Shapiro L, Love J, Colman DR (2007) Adhesion molecules in the nervous system: structural insights into function and diversity. Annu Rev Neurosci 30:451-474

    Article  PubMed  CAS  Google Scholar 

  6. Edelman GM, Crossing KL (1991) Cell adhesion molecules - implications for a molecular histology. Annu Rev Biochem 60:155-190

    Article  PubMed  CAS  Google Scholar 

  7. Lander ES, Linton LM, Birren B et al (2001) Initial sequencing and analysis of the human genome. Nature 409:860-921

    Article  PubMed  CAS  Google Scholar 

  8. Yoshihara Y, Oka S, Ikeda J et al (1991) Immunoglobulin superfamily molecules in the nervous system. Neurosci Res 10:83-105

    Article  PubMed  CAS  Google Scholar 

  9. Crocker PR, Kelm S, Hartnell A et al (1996) Sialoadhesin and related cellular recognition molecules of the immunoglobulin superfamily. Biochem Soc Trans 24:150-156

    PubMed  CAS  Google Scholar 

  10. Jørgensen OS, Bock E (1974) Brain-specific synaptosomal membrane proteins demonstrated by crossed immunoelectrophoresis. J Neurochem 23:879-880

    Article  PubMed  Google Scholar 

  11. 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 USA 73:577-581

    Article  PubMed  CAS  Google Scholar 

  12. Brackenbury R, Thiery JP, Rutishauser U (1977) Adhesion among neural cells in chick embryo an immunological assay for molecules involved in cell-cell binding. J Biol Chem 252:6835-6840

    PubMed  CAS  Google Scholar 

  13. 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 

  14. Livingston B, Jacobs JL, Glick MC et al (1988) Extended polysialic acid chains (n greater than 55) in glycoproteins from human neuroblastoma cells. J Biol Chem 263:9443-9448

    PubMed  CAS  Google Scholar 

  15. Acheson A, Sunshine JL, Rutishauser U (1991) NCAM polysialic acid can regulate both cell-cell and cell-substrate interactions. J Cell Biol 114:143-153

    Article  PubMed  CAS  Google Scholar 

  16. Michalides RB, Kwa D, Springall N et al (1994) NCAM and lung cancer. Int J Cancer Suppl 8:34-37

    Article  PubMed  CAS  Google Scholar 

  17. 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 56:101-118

    Article  PubMed  CAS  Google Scholar 

  18. Harpaz Y, Chothia C (1994) Many of the immunoglobulin superfamily domains in cell adhesion molecules and surface receptors belong to a new structural set which is close to that containing variable domains. J Mol Biol 238:528-539

    Article  PubMed  CAS  Google Scholar 

  19. Casasnovas JM, Stehle T, Liu JH et al (1998) A dimeric crystal structure for the N-terminal two domains of intercellular adhesion molecule-1. Proc Natl Acad Sci USA 95:4134-4139

    Article  PubMed  CAS  Google Scholar 

  20. Chothia C, Jones EY (1997) The molecular structure of cell adhesion molecules. Annu Rev Biochem 66:823-862

    Article  PubMed  CAS  Google Scholar 

  21. Streltsov VA, Varghese JN, Carmichael JA et al (2004) Structural evidence for evolution of shark Ig new antigen receptor variable domain antibodies from a cell-surface receptor. Proc Natl Acad Sci USA 101:12444-12449

    Article  PubMed  CAS  Google Scholar 

  22. Hynes RO (1990) Fibronectins. Springer, New York

    Google Scholar 

  23. Bork P, Downing AK, Kieffer B et al (1996) Structure and distribution of modules in extracellular proteins. Q Rev Biophys 29:119-167

    Article  PubMed  CAS  Google Scholar 

  24. Thomsen NK, Soroka V, Jensen PH et al (1996) The three-dimensional structure of the first domain of neural cell adhesion molecule. Nat Struct Biol 3:581-585

    Article  PubMed  CAS  Google Scholar 

  25. Jensen PH, Soroka V, Thomsen NK et al (1999) Structure and interactions of NCAM modules 1 and 2 - basic elements in neural cell adhesion. Nat Struct Biol 6:486-493

    Article  PubMed  CAS  Google Scholar 

  26. Atkins AR, Chung J, Deechongkit S et al (2001) Solution structure of the third immunoglobulin domain of the neural cell adhesion molecule N-CAM: can solution studies define the mechanism of homophilic binding? J Mol Biol 311:161-172

    Article  PubMed  CAS  Google Scholar 

  27. Kasper C, Rasmussen H, Kastrup JS et al (2000) Structural basis of cell-cell adhesion by NCAM. Nat Struct Biol 7:389-393

    Article  PubMed  CAS  Google Scholar 

  28. Soroka V, Kolkova K, Kastrup JS et al (2003) Structure and interactions of NCAM Ig1-2-3 suggest a novel zipper mechanism for homophilic adhesion. Structure 11:1291-1301

    Article  PubMed  CAS  Google Scholar 

  29. Atkins AR, Osborne MJ, Lashuel HA et al (1999) Association between the first two immunoglobulin-like domains of the neural cell adhesion molecule N-CAM. FEBS Lett 451:162-168

    Article  PubMed  CAS  Google Scholar 

  30. 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 NCAM. J Biol Chem 227:24676-24683

    Article  Google Scholar 

  31. Lahrtz F, Horstkorte R, Cremer H et al (1997) VASE-encoded peptide modifies NCAM- and L1-mediated neurite outgrowth. J Neurosci Res 50:62-68

    Article  PubMed  CAS  Google Scholar 

  32. 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 281:36052-36059

    Article  PubMed  CAS  Google Scholar 

  33. Kiselyov VV, Skladchikova G, Hinsby A et al (2003) Demonstration of a direct interaction between FGFR1 and NCAM and evidence for a regulatory role of ATP. Structure 11:691-701

    Article  PubMed  CAS  Google Scholar 

  34. Carafoli F, Saffell JL, Hohenester E (2008) Structure of the tandem fibronectin type 3 domains of neural cell adhesion molecule. J Mol Biol 377:524-534

    Article  PubMed  CAS  Google Scholar 

  35. Kunz B, Lierheimer R, Rader C et al (2002) Axonin-1/TAG-1 Mediates cell-cell adhesion by a cis-assited trans-interaction. J Biol Chem 277:4551-4557

    Article  PubMed  CAS  Google Scholar 

  36. Anderson AA, Kendal CE, Garcia-Maya M et al (2005) A peptide from the first fibronectin domain of NCAM acts as an inverse agonist and stimulates FGF receptor activation, neurite outgrowth and survival. J Neurochem 95:570-583

    Article  PubMed  CAS  Google Scholar 

  37. Jacobsen J, Kiselyov V, Bock E et al (2008) A peptide motif from the second fibronectin module of the neural cell adhesion molecule, NCAM, NLIKQDDGGSPIRHY, is a binding site for the FGF receptor. Neurochem Res 32(12):2532-2539

    Article  Google Scholar 

  38. Dickson G, Gower HJ, Barton CH et al (1987) Human muscle neural cell adhesion molecule (N-CAM): identification of a muscle-specific sequence in the extracellular domain. Cell 50:1119-1130

    Article  PubMed  CAS  Google Scholar 

  39. Rao Y, Wu X-F, Gariepy J et al (1992) Identification of a peptide sequence involved in homophilic binding in the neural cell adhesion molecule NCAM. J Cell Biol 118:937-949

    Article  PubMed  CAS  Google Scholar 

  40. Rao Y, Zhao X, Wu X-F et al (1993) Structural characterization of a homophilic binding site in the neural cell adhesion molecule. J Biol Chem 268:20630-20638

    PubMed  CAS  Google Scholar 

  41. Rao Y, Zhao X, Siu C-H (1994) Mechanisms of homophilic binding mediated by the neural cell adhesion molecule NCAM. J Biol Chem 269:27540-27548

    PubMed  CAS  Google Scholar 

  42. Ranheim TS, Edelman GM, Cunningham BA (1996) Homophilic adhesion mediated by the neural cell adhesion molecule involves multiple immunoglobulin domains. Proc Natl Acad Sci USA 93:4071-4075

    Article  PubMed  CAS  Google Scholar 

  43. Kiselyov VV, Berezin V, Maar T et al (1997) The first Ig-like NCAM domain is involved in both double reciprocal interaction with the second Ig-like NCAM domain and in heparin binding. J Biol Chem 272:10125-10134

    Article  PubMed  CAS  Google Scholar 

  44. Atkins AR, Osborne MJ, Lashuel HA et al (1999) Association between the first two immunoglobulin-like domains of the neural cell adhesion molecule N-CAM. FEBS Lett 451:162-168

    Article  PubMed  CAS  Google Scholar 

  45. Shapiro L, Fannon AM, Kwong PD et al (1995) Structural basis of cell-cell adhesion by cadherins. Nature 374:327-337

    Article  PubMed  CAS  Google Scholar 

  46. Kostrewa D, Brockhaus M, D’Arcy A et al (2001) X-ray structure of junctional adhesion molecule: structural basis for homophilic adhesion via a novel dimerization motif. EMBO J 20:4391-4398

    Article  PubMed  CAS  Google Scholar 

  47. Freigang J, Proba K, Leder L et al (2000) The crystal structure of the ligand binding module of axonin-1/TAG-1 suggests a zipper mechanism for neural cell adhesion. Cell 101:425-433

    Article  PubMed  CAS  Google Scholar 

  48. Cole GJ, Akenson R (1989) Identification of a heparin-binding domain of the neural cell adhesion molecule N-CAM using synthetic peptides. Neuron 2:1157-1165

    Article  PubMed  CAS  Google Scholar 

  49. Kulahin N, Rudenko O, Kiselyov V et al (2005) Modulation of the homophilic interaction between the first and second Ig modules of neural cell adhesion molecule by heparin. J Neurochem 95:46-55

    Article  PubMed  CAS  Google Scholar 

  50. Atkins AR, Gallin WJ, Owens GC et al (2004) Neural cell adhesion molecule (N-CAM) homophilic binding mediated by the two N-terminal Ig domains is influenced by intramolecular domain-domain interactions. J Biol Chem 279:49633-49643

    Article  PubMed  CAS  Google Scholar 

  51. Mörtl M, Sonderegger P, Diederichs K et al (2007) The crystal structure of the ligand-binding module of human TAG-1 suggests a new mode of homophilic interaction. Protein Sci 16:2174-2183

    Article  PubMed  Google Scholar 

  52. Johnson CP, Fujimoto I, Perrin-Tricaud C et al (2004) Mechanism of homophilic adhesion by the neural cell adhesion molecule: use of multiple domains and flexibility. Proc Natl Acad Sci USA 101:6963-6968

    Article  PubMed  CAS  Google Scholar 

  53. Wieland JA, Gewirth AA, Leckband DE (2005) Single molecule adhesion measurements reveal two homophilic neural cell adhesion molecule bonds with mechanically distinct properties. J Biol Chem 280:41037-41046

    Article  PubMed  CAS  Google Scholar 

  54. Kulahin N, Kasper C, Gajhede M et al (2004) Expression, crystallization and preliminary X-ray analysis of extracellular modules of the neural cell-adhesion molecules NCAM and L1. Acta Crystallogr D Biol Crystallogr 60:591-593

    Article  PubMed  Google Scholar 

  55. Wu H, Kwong PD, Hendrickson WA (1997) Dimeric association and segmental variability in the structure of human CD4. Nature 387:527-530

    Article  PubMed  CAS  Google Scholar 

  56. Su X-D, Gastinel LN, Vaughn DE et al (1998) Crystal structure of hemolin: a horseshoe shape with implications for homophilic adhesion. Science 281:991-995

    Article  PubMed  CAS  Google Scholar 

  57. Chen X, Kim TD, Carman CV et al (2007) Structural plasticity in Ig superfamily domain 4 of ICAM-1 mediates cell surface dimerization. Proc Natl Acad Sci USA 104:15358-15363

    Article  PubMed  CAS  Google Scholar 

  58. Johnson CP, Fragneto G, Konovalov O et al (2005) Structural studies of the neural-cell-adhesion molecule by X-ray and neutron reflectivity. Biochemistry 44:546-554

    Article  PubMed  CAS  Google Scholar 

  59. Hall AK, Rutishauser U (1987) Visualization of neural cell adhesion molecule by electron microscopy. J Cell Biol 104:1579-1586

    Article  PubMed  CAS  Google Scholar 

  60. Becker JW, Erickson HP, Hoffman S et al (1989) Topology of cell adhesion molecules. Proc Natl Acad Sci USA 86:1088-1092

    Article  PubMed  CAS  Google Scholar 

  61. Hunte C, Michel H (2002) Crystallisation of membrane proteins mediated by antibody fragments. Curr Opin Struct Biol 4:503-508

    Article  Google Scholar 

  62. Shea C, Bloedorn L, Sullivan MA (2005) Rapid isolation of single-chain antibodies for structural genomics. J Struct Funct Genomics 6:171-175

    Article  PubMed  CAS  Google Scholar 

  63. Rigaud J, Chami M, Lambert O et al (2000) Use of detergents in two-dimensional crystallization of membrane proteins. Biochim Biophys Acta 1508:112-128

    Article  PubMed  CAS  Google Scholar 

  64. Vink M, Derr K, Love J et al (2007) A high-throughput strategy to screen 2D crystallization trials of membrane proteins. Struct Biol 160:295-304

    Article  CAS  Google Scholar 

  65. Neylon C (2008) Small angle neutron and X-ray scattering in structural biology: recent examples from the literature. Eur Biophys J 37:531-541

    Article  PubMed  CAS  Google Scholar 

  66. Pickford AR, Campbell ID (2004) NMR studies of modular protein structures and their interactions. Chem Rev 104:3557-3566

    Article  PubMed  CAS  Google Scholar 

  67. J-H W, Springer TA (1998) Structural specializations of immunoglobulin superfamily members for adhesion to integrins and viruses. Immunol Rev 163:197-215

    Article  Google Scholar 

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Authors and Affiliations

  1. Novo Nordisk A/S, Novo Nordisk Park, G6 S.154012760, Måløv, Denmark

    Vladislav Soroka, Christina Kasper & Flemming M. Poulsen

Authors
  1. Vladislav Soroka
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  2. Christina Kasper
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  3. Flemming M. Poulsen
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Correspondence to Vladislav Soroka .

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Editors and Affiliations

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

    Vladimir Berezin

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Soroka, V., Kasper, C., Poulsen, F.M. (2010). Structural Biology of 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_1

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