Disease relevance of NRCAM

• To check the specificity of this aggregation, a fusion protein (FGTNr) consisting of glutathione S-transferase linked to the six immunoglobulin domains and the first fibronectin type III repeat of Nr-CAM was expressed in Escherichia coli [1].
• When tested as a substrate, Nr-Fc induced robust neurite outgrowth from dorsal root ganglion and sympathetic ganglion neurons, but it was not effective for tectal and forebrain neurons [2].

High impact information on NRCAM

• However, despite this fact and despite their ubiquitous expression in the spinal cord, NgCAM and NrCAM are selective binding partners for axonin-1 and F11 in sensory axon guidance [3].
• The present in vivo study demonstrates that interactions by two of these molecules, axonin-1 on commissural growth cones and Nr-CAM on floor plate cells, are required for accurate pathfinding at the midline [4].
• Under the reverse experimental conditions where NrCAM induces neurite extension, F11, and not neurofascin, serves as axonal receptor [5].
• Binding between the neural cell adhesion molecules axonin-1 and Nr-CAM/Bravo is involved in neuron-glia interaction [6].
• Together, these results implicate a binding between axonin-1 of the neuritic and Nr-CAM of the glial cell membrane in the early phase of axon ensheathment in the peripheral nervous system [6].

Biological context of NRCAM

• Bravo/Nr-CAM is closely related to the cell adhesion molecules L1 and Ng-CAM and has a similar heterodimer structure [7].
• After transfection, L cells expressed Nr-CAM on their surface and aggregated [1].
• The temporal expression of Nr-CAM was correlated with various neural morphoregulatory events, including cell proliferation and migration, axonal outgrowth and myelination [8].
• These anomalous observations are apparently not the result of differential sensitivity of the 23A7 epitope to fixation, the use of suboptimal concentrations of the MAb, or selective MAb binding to a subset of Bravo/Nr-CAM molecules produced by alternative splicing of the transcript or by posttranslational modification [9].

Anatomical context of NRCAM

• By antibody blockage experiments an axonin-1 receptor on the glial cells was identified as Nr-CAM [6].
• The results indicate that Nr-CAM is a cell adhesion molecule of the nervous system that can bind by two distinct mechanisms, a homophilic mechanism that can mediate interactions between neurons and a heterophilic mechanism that can mediate binding between neurons and other cells such as fibroblasts [1].
• To clarify the mode of action of Nr-CAM, a mouse fibroblast cell line L-M(TK-) (or L cells) was transfected with a DNA expression construct encoding an entire chicken Nr-CAM cDNA sequence [1].
• Nr-CAM also serves as a neuronal receptor for several other cell surface molecules, but its role as a ligand in neurite outgrowth is poorly understood [2].
• We studied this problem using a chimeric Fc-fusion protein of the extracellular region of Nr-CAM (Nr-Fc) and investigated potential neuronal receptors in the developing peripheral nervous system [2].

Associations of NRCAM with chemical compounds

• Nr-CAM is a membrane glycoprotein that is expressed on neurons [1].

Other interactions of NRCAM

• In vitro NgCAM and NrCAM were shown to bind to both axonin-1 and F11 [3].
• FAR-2 is binding to the Ig superfamily protein NgCAM/L1, but not to the related receptor NrCAM, and it is also interacting with the modular ECM protein tenascin-R [10].
• Neuron-glia-related cell adhesion molecule (Nr-CAM) is a recently characterized cell adhesion molecule in the family of immunoglobulin-related molecules of which the neural cell adhesion molecule, N-CAM, is the prototype [8].

Analytical, diagnostic and therapeutic context of NRCAM

• On Northern blots, nucleic acid probes for Nr-CAM recognized one major RNA species of approximately 7 kb and much lesser amounts of larger RNAs [11].
• A glycoprotein containing one major component of Mr 145,000 on SDS-PAGE was purified from brain by lentil lectin affinity chromatography and FPLC, and its amino-terminal sequence was identical to that predicted from the Nr-CAM cDNA [11].
• Binding studies using transfected COS7 cells and immunoprecipitations reveal a direct interaction between neurofascin and NrCAM [5].
• Single cell cultures show an enrichment of NrCAM in the distal axon and growth cone [12].
• To understand better the role of such molecules in development, we have examined the sites of synthesis and expression of Nr-CAM by means of in situ hybridization and immunohistochemistry [8].

References