Disease relevance of LOC396059

• These structural features of Ng-CAM provide a framework for understanding its multiple functions in neuron-neuron interactions, neurite fasciculation, and neuron-glia interactions [1].
• In contrast, in the PNS (for example, the dorsal root ganglion and sciatic nerve), Ng-CAM appeared early on both cell bodies and neurites, and it continued to be present on both in the adult, even in the presence of myelin [2].
• To identify such factors for Ng-CAM, the neuron-glia CAM, constructs containing portions of the 5' end of the Ng-CAM gene were examined for activity after transfection into N2A neuroblastoma and NIH3T3 cells [3].
• 9L/NgCAM cells, however, did not migrate away from the vasculature and, thus, this protein alone cannot be responsible for diffuse invasiveness of some gliomas [4].

High impact information on LOC396059

• The cell adhesion molecules L1, N-CAM and Ng-CAM have been implicated in cell-cell interactions among developing neural cells [5].
• 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 [6].
• In vitro NgCAM and NrCAM were shown to bind to both axonin-1 and F11 [6].
• In contrast, though perturbation of Ng-CAM produced a defasciculation of the commissural neurites, it did not affect their guidance across the floor plate [7].
• The enhanced neurite fasciculation after overexpression of NgCAM by adenoviral vectors indicates that NgCAM is the limiting component for the formation of the axonin-12/NgCAM2 complexes and, thus, neurite fasciculation in DRG neurons [8].

Chemical compound and disease context of LOC396059

• Neurite outgrowth by embryonic chick ciliary ganglion (CG) neurons in response to these Schwann cell molecules largely depends on several specific neuronal cell surface receptors: integrin beta 1-class ECM receptors, L1/NgCAM, and N-cadherin (Bixby et al.: Journal of Cell Biology 107:353-361 1988) [9].

Biological context of LOC396059

• Structure of the chicken neuron-glia cell adhesion molecule, Ng-CAM: origin of the polypeptides and relation to the Ig superfamily [1].
• The amino acid sequence of chicken Ng-CAM is most similar to that of mouse L1 but the overall identity is only 40% and Ng-CAM contains a short fibronectin-like segment with an RGD sequence that has no counterpart in L1 [1].
• The observations that a protein corresponding to F135 contains the cell aggregation sites whereas one corresponding to the F80 has the ability to promote neurite outgrowth suggest that proteolytic cleavage may be an important event in regulating these Ng-CAM activities during embryonic development and neural regeneration [10].
• Sciatic nerves of mouse mutants with defects in cell interactions showed abnormalities in the distribution patterns and amount of Ng-CAM, N-CAM, and cytotactin that were consistent with the known morphological nodal disorders [11].
• We present two possible models for the DM-GRASP-NgCAM association and a hypothesis for neural cell adhesion function that features the dimerization of cell adhesion molecules [12].

Anatomical context of LOC396059

• The axonal surface glycoproteins neuronglia cell adhesion molecule (NgCAM) and axonin-1 promote cell-cell adhesion, neurite outgrowth and fasciculation, and are involved in growth cone guidance [13].
• Ng-CAM was found on developing neurons at approximately the same time that neurofilaments first appear, times at which glial cells are still undergoing differentiation from neuroepithelial precursors [14].
• By 3 d in the chick embryo, the first neurons detected by antibodies to Ng-CAM are located in the ventral neural tube; these precursors of motor neurons emit well-stained fibers to the periphery [14].
• The earliest neurons in the PNS stained by anti-Ng-CAM appeared by 4 d of development in the cranial ganglia [14].
• Anti-Ng-CAM antibodies labeled neurites, Schwann cells and the endoneurial tubes in the distal stump [15].

Associations of LOC396059 with chemical compounds

• The neuron-glia cell adhesion molecule (Ng-CAM) mediates both neuron-neuron and neuron-glia adhesion; it is detected on SDS-PAGE as a predominant 135-kD glycoprotein, with minor components of 80, 190, and 210 kD [1].
• The cDNA sequence is continuous across the junction between the 135- and 80-kD components, and a single 170-kD Ng-CAM polypeptide was isolated from tunicamycin-treated cells [1].
• Much higher rates of aggregation were observed when the ratio of Ng-CAM to lipid in the liposome was increased [16].
• Moreover the NH2-terminal sequence of E587 shows similarity with L1 and Ng-CAM [17].
• In contrast, the rate of L1-mediated neurite outgrowth of rat postnatal day 6 cerebellar granule cells grown on a substratum of NgCAM, the chick homologue of L1, was inhibited by 48.6% in the presence of ethanol with a half-maximal concentration of 4.7 mM [18].

Physical interactions of LOC396059

• 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 [19].

Other interactions of LOC396059

• The present findings and those of previous studies suggest that together the neural cell adhesion molecule and Ng-CAM mediate specific cellular interactions during the formation of neuronal networks by means of modulation events that govern their prevalence and polarity on neuronal cell surfaces [14].
• Neural CAM (N-CAM), liver CAM (L-CAM), and neuron-glia CAM (Ng-CAM), as well as substrate molecules (laminin and fibronectin), were compared in newborn chicken skin by immunohistochemical means [20].
• Positive regulatory elements active in both cell types included an Ng-CAM proximal promoter with SP1 and cAMP response element motifs extending 447 base pairs upstream of a single RNA start site and a region within the first exon corresponding to 5'-untranslated sequences [3].
• Further, high levels of N-CAM, Ng-CAM, and N-cadherin were uniformly expressed throughout the entire olfactory nerve while migrating LHRH neurons were confined to the medial half of the nerve [21].

Analytical, diagnostic and therapeutic context of LOC396059

• Ultrastructural immunogold techniques indicated that both N-CAM and Ng-CAM were enriched in the nodal axoplasm and axolemma of myelinated fibers as well as within the nodal regions of the myelinating Schwann cell [11].
• By using higher resolution immunoelectron microscopy, the present study has also revealed new information on the subcellular localization of Ng-CAM on developing spinal interneurons, neuroepithelial cells, and floor plate cells [22].
• Here we test the roles of L1/NgCAM, beta1 integrin, and cadherins, using a coculture system in which embryonic chick brainstem neurons regenerate axons into an explant of embryonic spinal cord [23].
• Using immunohistochemistry and in situ hybridization we show that during the period when neurons lose their regenerative capacity they reduce expression of mRNA for N-cadherin, and reduce axonal L1/NgCAM protein through a post-transcriptional mechanism [23].

References