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Gene Review

NCAM1  -  neural cell adhesion molecule 1

Gallus gallus

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Disease relevance of ANKK1

  • The B1A3 mAb recognizes a 25,000-D heparin-binding fragment derived from chicken N-CAM, and also binds to a 65,000-D fragment, presumably Frl, produced by digestion of N-CAM with Staphylococcus aureus V8 protease [1].
  • Using a neuroblastoma line to study functional differences between embryonic and adult BSP-2/N-CAM molecules, we show here that liposomes bearing adult BSP-2 but not those bearing the embryonic form adhere to neuroblastoma cells, demonstrating that the two forms do indeed possess different binding properties [2].
  • This enhancement of fasciculation was reversed by addition of anti-NCAM Fab, suggesting that the enzyme treatment was not toxic and did not produce nonspecific effects on adhesion [3].
  • Rabbit polyclonal antibodies directed against the chicken neural cell adhesion molecule (N-CAM) were used to isolate four overlapping cDNA clones from a chicken cDNA expression library in bacteriophage gamma gt11 [4].
  • In contrast, the N-CAM autolysis products released along with Fr1 neither bound to cells nor competed for N-CAM binding [5].

Psychiatry related information on ANKK1

  • The effect of C3 on memory consolidation was similar to that obtained with anti-NCAM as the amnesia was not observed until the 48-h recall time [6].
  • A synthetic peptide ligand of neural cell adhesion molecule (NCAM) IgI domain prevents NCAM internalization and disrupts passive avoidance learning [6].

High impact information on ANKK1

  • Recently, a membrane glycoprotein called neural cell adhesion molecule (N-CAM) has been characterized in chick and rodent nervous tissue that appears to act as a ligand in adhesion among neural cell bodies or neurites [2].
  • We have identified a mouse neural surface glycoprotein, named BSP-2 (ref. 7), which by criteriaof electrophoretic migration, developmental changes, amino acid and sugar composition seems to be closely related or identical to N-CAM [2].
  • In contrast to the polysialic acid (PSA)-dependent cooperative streaming migration of olfactory neuronal precursors, the migration of oligodendrocyte precursors along the optic nerve appeared axophilic and unaffected by removal of neural cell adhesion molecule (N-CAM)-associated PSA [7].
  • Regulation and activity-dependence of N-cadherin, NCAM isoforms, and polysialic acid on chick myotubes during development [8].
  • We show here that during this process N-cadherin and the different structural forms of NCAM are regulated in a pattern that involves both temporal changes in expression and localization to particular regions of the muscle cell surface [8].

Chemical compound and disease context of ANKK1


Biological context of ANKK1

  • Studies on L cells transfected with NCAM mutant cDNAs using cell aggregation and NCAM-covasphere binding assays indicate that the third immunoglobulin-like domain is involved in homophilic binding [10].
  • These results define two additional modes by which N-CAM expression can be modulated: by RNA splicing at a new site and by differential membrane attachment of the resulting polypeptide through a lipid intermediate [11].
  • The chick neural cell adhesion molecule, CAM, is a cell-surface protein specific to the nervous system and has been implicated in cell adhesion among cells and neurites of the developing retina and brain [12].
  • These results are consistent with the hypothesis that the major binding protein for NCAM is NCAM itself, and suggest that differences in polysialic acid content do not directly alter the properties of NCAM's homophilic binding site [13].
  • These results provide the first direct evidence that the polysialic acid on NCAM has a regulatory effect on adhesion between living cells, and that the amount of this carbohydrate is critical for the normal morphogenesis of nerve tissue [3].

Anatomical context of ANKK1

  • N-CAM is lost from the nerves as myelination proceeds, and from myotubes as they mature [14].
  • An assay has been designed for the identification of NCAM-binding proteins present in an NP-40 detergent extract of brain membranes [13].
  • We propose that NCAM-mediated adhesion promotes contact between cell membranes to allow the transmission of an otherwise NCAM-independent signal [15].
  • In addition, N-CAM is present on the surfaces of motor nerve terminals and of Schwann cells that cap nerve terminals, but absent from myelinated portions of motor axons and from myelinating Schwann cells [14].
  • Taken together with the previous studies (Rieger, F., M. Grumet, and G. M. Edelman, J. Cell Biol. 101:285-293), these data suggest that local signals between neurons and glia may regulate CAM expression in the spinal cord and nerve during regeneration, and that activity may regulate N-CAM expression in muscle [16].

Associations of ANKK1 with chemical compounds

  • The neural cell adhesion molecule N-CAM is an intrinsic membrane glycoprotein that is expressed in the embryonic chicken nervous system as two different polypeptide chains encoded by alternatively spliced transcripts of a single gene [17].
  • In the present study we have determined the topographic localization of the heparin-binding fragment from N-CAM, which has been identified by our laboratory [1].
  • During normal development, the neural cell adhesion molecule N-CAM changes at the cell-surface from a sialic acid-rich embryonic, or E form, to several adult, or A forms that have less sialic acid (E-to-A conversion) [18].
  • These results indicated that the tubulin and actin cytoskeletons were not critically required for adhesion to NCAM and make it unlikely that the cell surface ligand for NCAM is an integrin [19].
  • In order to understand the mechanism of these changes, a cyanogen bromide (CNBr) fragment that contained 90% of the sialic acid of N-CAM was isolated and characterized according to the number of carbohydrate attachment sites and reactivity with specific monoclonal antibodies [20].

Physical interactions of ANKK1

  • In the present study we have characterized the major proteoglycans of chick brain, focusing on their pattern of expression in development and on identifying the heparan sulfate proteoglycan (HSPG) that binds to the neural cell adhesion molecule (NCAM) [21].

Regulatory relationships of ANKK1


Other interactions of ANKK1


Analytical, diagnostic and therapeutic context of ANKK1


  1. Topographic localization of the heparin-binding domain of the neural cell adhesion molecule N-CAM. Cole, G.J., Loewy, A., Cross, N.V., Akeson, R., Glaser, L. J. Cell Biol. (1986) [Pubmed]
  2. Adult and embryonic mouse neural cell adhesion molecules have different binding properties. Sadoul, R., Hirn, M., Deagostini-Bazin, H., Rougon, G., Goridis, C. Nature (1983) [Pubmed]
  3. Specific alteration of NCAM-mediated cell adhesion by an endoneuraminidase. Rutishauser, U., Watanabe, M., Silver, J., Troy, F.A., Vimr, E.R. J. Cell Biol. (1985) [Pubmed]
  4. Alternatively spliced mRNAs code for different polypeptide chains of the chicken neural cell adhesion molecule (N-CAM). Murray, B.A., Hemperly, J.J., Prediger, E.A., Edelman, G.M., Cunningham, B.A. J. Cell Biol. (1986) [Pubmed]
  5. Molecular topography of the neural cell adhesion molecule N-CAM: surface orientation and location of sialic acid-rich and binding regions. Cunningham, B.A., Hoffman, S., Rutishauser, U., Hemperly, J.J., Edelman, G.M. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  6. A synthetic peptide ligand of neural cell adhesion molecule (NCAM) IgI domain prevents NCAM internalization and disrupts passive avoidance learning. Foley, A.G., Hartz, B.P., Gallagher, H.C., Rønn, L.C., Berezin, V., Bock, E., Regan, C.M. J. Neurochem. (2000) [Pubmed]
  7. Focal ventricular origin and migration of oligodendrocyte precursors into the chick optic nerve. Ono, K., Yasui, Y., Rutishauser, U., Miller, R.H. Neuron (1997) [Pubmed]
  8. Regulation and activity-dependence of N-cadherin, NCAM isoforms, and polysialic acid on chick myotubes during development. Fredette, B., Rutishauser, U., Landmesser, L. J. Cell Biol. (1993) [Pubmed]
  9. A role for a chicken homolog of the neural cell adhesion molecule L1 in consolidation of memory for a passive avoidance task in the chick. Scholey, A.B., Mileusnic, R., Schachner, M., Rose, S.P. Learn. Mem. (1995) [Pubmed]
  10. Identification of a peptide sequence involved in homophilic binding in the neural cell adhesion molecule NCAM. Rao, Y., Wu, X.F., Gariepy, J., Rutishauser, U., Siu, C.H. J. Cell Biol. (1992) [Pubmed]
  11. cDNA clones of the neural cell adhesion molecule (N-CAM) lacking a membrane-spanning region consistent with evidence for membrane attachment via a phosphatidylinositol intermediate. Hemperly, J.J., Edelman, G.M., Cunningham, B.A. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  12. Antibodies to a neural cell adhesion molecule disrupt histogenesis in cultured chick retinae. Buskirk, D.R., Thiery, J.P., Rutishauser, U., Edelman, G.M. Nature (1980) [Pubmed]
  13. Binding properties of detergent-solubilized NCAM. Hall, A.K., Nelson, R., Rutishauser, U. J. Cell Biol. (1990) [Pubmed]
  14. Distribution of N-CAM in synaptic and extrasynaptic portions of developing and adult skeletal muscle. Covault, J., Sanes, J.R. J. Cell Biol. (1986) [Pubmed]
  15. Neural cell adhesion molecule regulates cell contact-mediated changes in choline acetyltransferase activity of embryonic chick sympathetic neurons. Acheson, A., Rutishauser, U. J. Cell Biol. (1988) [Pubmed]
  16. Altered expression of neuronal cell adhesion molecules induced by nerve injury and repair. Daniloff, J.K., Levi, G., Grumet, M., Rieger, F., Edelman, G.M. J. Cell Biol. (1986) [Pubmed]
  17. Cell surface modulation of the neural cell adhesion molecule resulting from alternative mRNA splicing in a tissue-specific developmental sequence. Murray, B.A., Owens, G.C., Prediger, E.A., Crossin, K.L., Cunningham, B.A., Edelman, G.M. J. Cell Biol. (1986) [Pubmed]
  18. Conversion of embryonic form to adult forms of N-CAM in vitro: results from de novo synthesis of adult forms. Friedlander, D.R., Brackenbury, R., Edelman, G.M. J. Cell Biol. (1985) [Pubmed]
  19. Evidence for heterophilic adhesion of embryonic retinal cells and neuroblastoma cells to substratum-adsorbed NCAM. Murray, B.A., Jensen, J.J. J. Cell Biol. (1992) [Pubmed]
  20. Mapping of three carbohydrate attachment sites in embryonic and adult forms of the neural cell adhesion molecule. Crossin, K.L., Edelman, G.M., Cunningham, B.A. J. Cell Biol. (1984) [Pubmed]
  21. Analysis of proteoglycan expression in developing chicken brain: characterization of a heparan sulfate proteoglycan that interacts with the neural cell adhesion molecule. Burg, M.A., Halfter, W., Cole, G.J. J. Neurosci. Res. (1995) [Pubmed]
  22. Initial appearance and regional distribution of the neuron-glia cell adhesion molecule in the chick embryo. Thiery, J.P., Delouvée, A., Grumet, M., Edelman, G.M. J. Cell Biol. (1985) [Pubmed]
  23. Expression patterns of the cell adhesion molecule Nr-CAM during histogenesis of the chick nervous system. Krushel, L.A., Prieto, A.L., Cunningham, B.A., Edelman, G.M. Neuroscience (1993) [Pubmed]
  24. Calcium-activated proteolysis of intracellular domains in the cell adhesion molecules NCAM and N-cadherin. Covault, J., Liu, Q.Y., el-Deeb, S. Brain Res. Mol. Brain Res. (1991) [Pubmed]
  25. The recognition memory of imprinting: biochemistry and electrophysiology. McCabe, B.J., Nicol, A.U. Behav. Brain Res. (1999) [Pubmed]
  26. Cell adhesion molecules in early chicken embryogenesis. Thiery, J.P., Duband, J.L., Rutishauser, U., Edelman, G.M. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
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