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

• We suggest that interocular feature matching can attenuate the potency of interocular suppression, but unlike in previous work (McKee, S. P., Bravo, M. J., Taylor, D. G., & Legge, G. E. (1994) Stereo matching precedes dichoptic masking. Vision Research, 34, 1047) we do not invoke a special role for depth perception [5].
• Mutations in L1CAM, the gene encoding the L1 neuronal cell adhesion molecule, lead to an X-linked trait characterized by one or more of the symptoms of hydrocephalus, adducted thumbs, agenesis or hypoplasia of corpus callosum, spastic paraplegia, and mental retardation (L1-disease) [6].
• Polymorphisms in NrCAM have been reported to be associated with autism susceptibility and with substance abuse, implicating NrCAM in reward circuitry [7].

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

• The most commonly occurring sialic acid, N-acetylneuraminic acid, is the repeating unit in polysialic acid chain of human neuronal cell adhesion molecule as well as in capsular polysialic acid of neuroinvasive bacteria, Escherichia coli K1 and Neisseria meningitidis [10].
• While Salmonella serovars Typhimurium and Heidelberg grew in the fungicide Bravo, and Enteritidis grew in the insecticide Vendex within 96 h at 21 degrees C in the laboratory, pathogen growth in other pesticide formulations did not occur [11].

Biological context of NRCAM

• By human-chick sequence comparison we identified exons not previously found in mammalian NRCAM mRNAs [12].
• Nr-CAM: a cell adhesion molecule with ligand and receptor functions [13].
• Alternative splicing of human NrCAM in neural and nonneural tissues [14].
• Characterization of a highly conserved human homolog to the chicken neural cell surface protein Bravo/Nr-CAM that maps to chromosome band 7q31 [15].
• Fluorescence in situ hybridization maps the gene for human Bravo/Nr-CAM to human chromosome 7q31.1-q31 [15].

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

• These results suggest that binding of glial RPTPbeta to the contactin/Nr-CAM complex is important for neurite growth and neuronal differentiation [18].

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

• F3Fc-conjugated microspheres binding to neuronal growth cones resulted from heterophilic interaction with NrCAM but not with L1 [29].
• Previous studies with high-resolution two-dimensional gel electrophoresis identified 58 [35S]methionine-labeled polypeptides common to human epithelial amnion cells and lung fibroblasts, whose rate of synthesis is sensitive to neoplastic transformation [Bravo, R. & Celis, J. (1982) Clin. Chem. (Winston-Salem, NC) 28, 949-955] [30].
• METHODS: CSF N-CAM was measured by the Western blot technique in 45 DSM-III-R diagnosed male schizophrenic patients both on and off haloperidol treatment and in 20 healthy male control subjects [31].
• Sequence analysis indicated that this sequence is identical to the previously isolated human neuron-glia-related cell adhesion molecule hNr-CAM [32].
• Gene-specific RT-PCR analysis indicated that hNr-CAM is over-expressed in high-grade astrocytomas, gliomas and glioblastoma tumor tissues as compared to normal brain tissue [32].

References