Disease relevance of Nrcam

• Using optical tweezers and single particle tracking of beads coated with the ligand TAG-1, we analyzed the mobility of NrCAM-deletion mutants transfected in a neuroblastoma cell line [1].
• To examine the potential role of Nr-CAM in this process, we treated myelinating cocultures of DRG (dorsal root ganglion) neurons and Schwann cells with an Nr-CAM-Fc (Nr-Fc) fusion protein [2].

Psychiatry related information on Nrcam

• These observations support NrCAM as a positionally cloned and drug-regulated gene whose variants are likely to change expression and alter substance abuse vulnerabilities in human addictions and animal models of drug reward [3].

High impact information on Nrcam

• Furthermore, both neurofascin and the related molecule Nr-CAM are tyrosine phosphorylated in a developmentally regulated pattern in rat brain [4].
• Molecular composition of the node of Ranvier: identification of ankyrin-binding cell adhesion molecules neurofascin (mucin+/third FNIII domain-) and NrCAM at nodal axon segments [5].
• NrCAM coupling to the cytoskeleton depends on multiple protein domains and partitioning into lipid rafts [1].
• Next, we showed that the actin-dependent retrograde movement of NrCAM required partitioning into lipid rafts as indicated by cholesterol depletion experiments using methyl-beta-cyclodextrin [1].
• Nr-Fc had no effect on initial axon-Schwann cell interactions, including Schwann cell proliferation, or on the extent of myelination, but it strikingly and specifically inhibited Na(+) channel and ankyrin G accumulation at the node [2].

Biological context of Nrcam

• Neurone glial-related cell adhesion molecule (NrCAM) is a member of the L1 family of transmembrane cell adhesion receptors which are involved in the development and function of the mammalian nervous system [6].
• NrCAM displays haplotype-specific gene expression in human post-mortem brain samples [3].
• Fine mapping within a chromosome 7 region that contains previously linked and associated genomic markers identifies NrCAM haplotypes that are associated with substance abuse vulnerabilities in four samples of abusers and controls [3].
• Furthermore Nr-CAM, which is widely expressed in the cerebellum during embryonic development, becomes strictly confined to Purkinje and Golgi cells in postnatal cerebellum, suggesting a possible role of Nr-CAM for the maturation or stabilization of the synaptic contacts, in particular between climbing fibers and Purkinje cells [7].

Anatomical context of Nrcam

• Additionally, NrCAM constructs whose last three amino acids had been deleted appeared to have a dominant negative effect on neurite extension of cerebellar granule cells [6].
• NrCAM, visualized with antibodies specific for the ecto-domain, also was found to be coexpressed with neurofascin at nodes of Ranvier and at axon initial segments [5].

Physical interactions of Nrcam

• We identified synapse associated protein 102 (SAP102) as a new binding partner for NrCAM [6].
• Nr-Fc bound directly to neurons and clustered and coprecipitated neurofascin expressed on axons [2].

Other interactions of Nrcam

• This is the first interaction reported for NrCAM, and its association with SAP102 suggests that it is part of a larger complex which can interact with many different signalling pathways [6].

References