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Gene Review

NRCAM  -  neuronal cell adhesion molecule

Homo sapiens

Synonyms: Bravo, KIAA0343, Neuronal cell adhesion molecule, Neuronal surface protein Bravo, Ng-CAM-related, ...
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Disease relevance of NRCAM

  • Dominant negative LEF-1 decreased Nr-CAM expression and antibodies to Nr-CAM inhibited the motility of B16 melanoma cells [1].
  • Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis [1].
  • Cataracts, the most common cause of visual impairment, are generated in NrCAM-deficient mice by a disorganization of lens fibers, followed by cellular disintegration and accumulation of cellular debris [2].
  • Moreover, Nr-CAM was found in complex with alpha4beta1 integrins in melanoma cells, indicating that it can mediate, in addition to homophilic cell-cell adhesion, heterophilic adhesion with extracellular matrix receptors [3].
  • There is convincing in vitro evidence that the muscular form of the nicotinic acetylcholine receptor (nAChR), the neuronal cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR) bind rabies virus and/or facilitate rabies virus entry into cells [4].

Psychiatry related information on NRCAM


High impact information on NRCAM

  • Retroviral transduction of Nr-CAM into NIH3T3 cells stimulated cell growth, enhanced motility, induced transformation, and produced rapidly growing tumors in nude mice [1].
  • In this issue of Neuron, a study by Williams et al. shows that the cell adhesion molecule Nr-CAM facilitates/promotes the decussation of contralateral axons across the chiasm [8].
  • Interference with axonin-1 and NrCAM interactions unmasks a floor-plate activity inhibitory for commissural axons [9].
  • The perturbation of NrCAM interactions also resulted in an avoidance of the floor plate, but without inducing growth-cone collapse [9].
  • We reveal that the absence of NrCAM causes the formation of mature cataracts in the mouse, whereas significant pathfinding errors of commissural axons at the midline of the spinal cord or of proprioceptive axon collaterals are not detected [2].

Chemical compound and disease context of NRCAM


Biological context of NRCAM


Anatomical context of NRCAM

  • These results indicate that neither L1 nor NrCAM are required for TAG-1-elicited neurite outgrowth [16].
  • Nr-CAM Ng-CAM-related cell adhesion molecule) is expressed only in the nervous system on a subset of neurons and non-neuronal cells, including floor-plate cells in the spinal cord and Schwann cells [13].
  • Furthermore, we show that NrCAM is expressed at significant levels outside the nervous system; in particular in pancreas, adrenal glands, and placenta and that expression in both brain and other tissues is accompanied by a very variable pattern of exon utilization in fetal and adult cells [14].
  • Chicken Bravo/Nr-CAM has been shown to interact with other cell surface molecules of the Ig superfamily and has been implicated in specific pathfinding roles of axonal growth cones in the developing nervous system [15].
  • Identification of endothelial cell genes expressed in an in vitro model of angiogenesis: induction of ESM-1, (beta)ig-h3, and NrCAM [17].

Associations of NRCAM with chemical compounds

  • Induction of neurite outgrowth through contactin and Nr-CAM by extracellular regions of glial receptor tyrosine phosphatase beta [18].
  • Analysis of neutron and gamma-ray streaming along the maze of NRCAM thallium production target room [19].
  • The neuronal cell adhesion molecule L1 (L1CAM) is a transmembrane glycoprotein belonging to the immunoglobulin superfamily and is essential in the development of the nervous system [20].
  • Differential overexpression of RTPZ was accompanied by that of its modulators pleiotrophin, NrCAM, tenascin, and the chondroitin sulfate proteoglycans, suggesting the importance of RTPZ signaling to WMPCs [21].
  • The activity of the transcription factor NF-kappaB can be modulated by members of the Rho family of small GTPases (Perona, R., Montaner, S., Saniger, L., Sánchez-Pérez, I., Bravo, R., and Lacal, J. C. (1997) Genes Dev. 11, 463-475) [22].

Physical interactions of NRCAM


Regulatory relationships of NRCAM

  • We have shown previously that F11 promotes neurite extension of chick tectal neurons by interaction with the tectal receptor NrCAM, a member of the L1 subgroup of the Ig superfamily [23].
  • Cellular binding assays support the possibility that the interaction of F11 to NrCAM is blocked in the presence of tenascin-R and tenascin-C [24].

Other interactions of NRCAM

  • The possible role of IMMP2L and several other candidate genes within the region of chromosomal rearrangement, including NRCAM, Leu-Rch Rep, and Reelin, is discussed [25].
  • CONCLUSIONS: NRCAM, LRRN3, KIAA0716 are unlikely to be involved in autism [26].
  • One of these encodes a premature stop codon that would give rise to an isoform of NRCAM lacking ankyrin-binding capacity [12].
  • Association was also detected for several polymorphisms in the promoter and untranslated region of NRCAM, suggesting that alterations in expression of this gene may be linked to autism susceptibility [27].
  • The Ig cell adhesion molecules (CAM) neurofascin (NF) and Nr-CAM are localized at developing nodes of Ranvier in peripheral myelinated axons prior to clustering of Na(+) channels [28].

Analytical, diagnostic and therapeutic context of NRCAM


  1. Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis. Conacci-Sorrell, M.E., Ben-Yedidia, T., Shtutman, M., Feinstein, E., Einat, P., Ben-Ze'ev, A. Genes Dev. (2002) [Pubmed]
  2. Targeted ablation of NrCAM or ankyrin-B results in disorganized lens fibers leading to cataract formation. Moré, M.I., Kirsch, F.P., Rathjen, F.G. J. Cell Biol. (2001) [Pubmed]
  3. The shed ectodomain of Nr-CAM stimulates cell proliferation and motility, and confers cell transformation. Conacci-Sorrell, M., Kaplan, A., Raveh, S., Gavert, N., Sakurai, T., Ben-Ze'ev, A. Cancer Res. (2005) [Pubmed]
  4. Rabies virus receptors. Lafon, M. J. Neurovirol. (2005) [Pubmed]
  5. Interocular suppression is gated by interocular feature matching. Meese, T.S., Hess, R.F. Vision Res. (2005) [Pubmed]
  6. Spectrum and detection rate of L1CAM mutations in isolated and familial cases with clinically suspected L1-disease. Finckh, U., Schröder, J., Ressler, B., Veske, A., Gal, A. Am. J. Med. Genet. (2000) [Pubmed]
  7. Association analysis of the NrCAM gene in autism and in subsets of families with severe obsessive-compulsive or self-stimulatory behaviors. Sakurai, T., Ramoz, N., Reichert, J.G., Corwin, T.E., Kryzak, L., Smith, C.J., Silverman, J.M., Hollander, E., Buxbaum, J.D. Psychiatr. Genet. (2006) [Pubmed]
  8. Under the eye of Nr-CAM. Nguyen-Ba-Charvet, K.T., Chédotal, A. Neuron (2006) [Pubmed]
  9. Interference with axonin-1 and NrCAM interactions unmasks a floor-plate activity inhibitory for commissural axons. Stoeckli, E.T., Sonderegger, P., Pollerberg, G.E., Landmesser, L.T. Neuron (1997) [Pubmed]
  10. Cloning, expression, and characterization of sialic acid synthases. Hao, J., Balagurumoorthy, P., Sarilla, S., Sundaramoorthy, M. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  11. Survival of pathogenic bacteria in pesticide solutions and on treated tomato plants. Guan, T.T., Blank, G., Holley, R.A. J. Food Prot. (2005) [Pubmed]
  12. The complete sequence of the human locus for NgCAM-related cell adhesion molecule reveals a novel alternative exon in chick and man and conserved genomic organization for the L1 subfamily. Dry, K., Kenwrick, S., Rosenthal, A., Platzer, M. Gene (2001) [Pubmed]
  13. Nr-CAM: a cell adhesion molecule with ligand and receptor functions. Grumet, M. Cell Tissue Res. (1997) [Pubmed]
  14. Alternative splicing of human NrCAM in neural and nonneural tissues. Wang, B., Williams, H., Du, J.S., Terrett, J., Kenwrick, S. Mol. Cell. Neurosci. (1998) [Pubmed]
  15. Characterization of a highly conserved human homolog to the chicken neural cell surface protein Bravo/Nr-CAM that maps to chromosome band 7q31. Lane, R.P., Chen, X.N., Yamakawa, K., Vielmetter, J., Korenberg, J.R., Dreyer, W.J. Genomics (1996) [Pubmed]
  16. Analysis of interactions of the adhesion molecule TAG-1 and its domains with other immunoglobulin superfamily members. Pavlou, O., Theodorakis, K., Falk, J., Kutsche, M., Schachner, M., Faivre-Sarrailh, C., Karagogeos, D. Mol. Cell. Neurosci. (2002) [Pubmed]
  17. Identification of endothelial cell genes expressed in an in vitro model of angiogenesis: induction of ESM-1, (beta)ig-h3, and NrCAM. Aitkenhead, M., Wang, S.J., Nakatsu, M.N., Mestas, J., Heard, C., Hughes, C.C. Microvasc. Res. (2002) [Pubmed]
  18. Induction of neurite outgrowth through contactin and Nr-CAM by extracellular regions of glial receptor tyrosine phosphatase beta. Sakurai, T., Lustig, M., Nativ, M., Hemperly, J.J., Schlessinger, J., Peles, E., Grumet, M. J. Cell Biol. (1997) [Pubmed]
  19. Analysis of neutron and gamma-ray streaming along the maze of NRCAM thallium production target room. Raisali, G., Hajiloo, N., Hamidi, S., Aslani, G. Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine. (2006) [Pubmed]
  20. L1-associated diseases: clinical geneticists divide, molecular geneticists unite. Fransen, E., Van Camp, G., Vits, L., Willems, P.J. Hum. Mol. Genet. (1997) [Pubmed]
  21. Complementary patterns of gene expression by human oligodendrocyte progenitors and their environment predict determinants of progenitor maintenance and differentiation. Sim, F.J., Lang, J.K., Waldau, B., Roy, N.S., Schwartz, T.E., Pilcher, W.H., Chandross, K.J., Natesan, S., Merrill, J.E., Goldmanm, S.A. Ann. Neurol. (2006) [Pubmed]
  22. Activation of serum response factor by RhoA is mediated by the nuclear factor-kappaB and C/EBP transcription factors. Montaner, S., Perona, R., Saniger, L., Lacal, J.C. J. Biol. Chem. (1999) [Pubmed]
  23. Functional cooperation of beta1-integrins and members of the Ig superfamily in neurite outgrowth induction. Treubert, U., Brümmendorf, T. J. Neurosci. (1998) [Pubmed]
  24. Functional interactions of the immunoglobulin superfamily member F11 are differentially regulated by the extracellular matrix proteins tenascin-R and tenascin-C. Zacharias, U., Nörenberg, U., Rathjen, F.G. J. Biol. Chem. (1999) [Pubmed]
  25. Disruption of a novel gene (IMMP2L) by a breakpoint in 7q31 associated with Tourette syndrome. Petek, E., Windpassinger, C., Vincent, J.B., Cheung, J., Boright, A.P., Scherer, S.W., Kroisel, P.M., Wagner, K. Am. J. Hum. Genet. (2001) [Pubmed]
  26. Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes. Hutcheson, H.B., Olson, L.M., Bradford, Y., Folstein, S.E., Santangelo, S.L., Sutcliffe, J.S., Haines, J.L. BMC Med. Genet. (2004) [Pubmed]
  27. Mutation screening and association analysis of six candidate genes for autism on chromosome 7q. Bonora, E., Lamb, J.A., Barnby, G., Sykes, N., Moberly, T., Beyer, K.S., Klauck, S.M., Poustka, F., Bacchelli, E., Blasi, F., Maestrini, E., Battaglia, A., Haracopos, D., Pedersen, L., Isager, T., Eriksen, G., Viskum, B., Sorensen, E.U., Brondum-Nielsen, K., Cotterill, R., Engeland, H., Jonge, M., Kemner, C., Steggehuis, K., Scherpenisse, M., Rutter, M., Bolton, P.F., Parr, J.R., Poustka, A., Bailey, A.J., Monaco, A.P. Eur. J. Hum. Genet. (2005) [Pubmed]
  28. Neurofascin interactions play a critical role in clustering sodium channels, ankyrin(G) and betaIV spectrin at peripheral nodes of Ranvier. Koticha, D., Maurel, P., Zanazzi, G., Kane-Goldsmith, N., Basak, S., Babiarz, J., Salzer, J., Grumet, M. Dev. Biol. (2006) [Pubmed]
  29. NrCAM, cerebellar granule cell receptor for the neuronal adhesion molecule F3, displays an actin-dependent mobility in growth cones. Faivre-Sarrailh, C., Falk, J., Pollerberg, E., Schachner, M., Rougon, G. J. Cell. Sci. (1999) [Pubmed]
  30. Changes in the relative proportion of transformation-sensitive polypeptides in giant HeLa cells produced by irradiation with lethal doses of x-rays. Bellatin, J., Bravo, R., Celis, J.E. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  31. Further studies of elevated cerebrospinal fluid neuronal cell adhesion molecule in schizophrenia. van Kammen, D.P., Poltorak, M., Kelley, M.E., Yao, J.K., Gurklis, J.A., Peters, J.L., Hemperly, J.J., Wright, R.D., Freed, W.J. Biol. Psychiatry (1998) [Pubmed]
  32. Cell adhesion molecule Nr-CAM is over-expressed in human brain tumors. Sehgal, A., Boynton, A.L., Young, R.F., Vermeulen, S.S., Yonemura, K.S., Kohler, E.P., Aldape, H.C., Simrell, C.R., Murphy, G.P. Int. J. Cancer (1998) [Pubmed]
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