Disease relevance of NCAM1

• 2. TPARM as well as NCAM1 and DRD2 were predicted to be candidate tumor suppressor genes within the commonly deleted region of malignant melanoma on 11q23.1-q23.2 (between microsatellite markers D11S1347 and D11S4122) [1].
• Expression of the polysialated form of NCAM has been also demonstrated in some malignant tumors, such as Wilms' tumor and small cell lung cancer [2].
• Retinoic acid-induced changes in polysialyltransferase mRNA expression and NCAM polysialylation in human neuroblastoma cells [3].
• RESULTS: CD56 revealed the most diffuse and intense positive staining, which was noted along the cell borders, in all specimens compared with other neuroendocrine tumor markers [4].
• RESULTS: For neural cell adhesion molecule, six of eight basal cell carcinomas and two of eight cutaneous squamous cell carcinomas stained positive [5].

Psychiatry related information on NCAM1

• We therefore undertook genetic analysis of NCAM1 in mood disorders [6].
• Neural cell adhesion molecule in human serum. Increased levels in dementia of the Alzheimer type [7].
• A locus for X-linked hydrocephalus (HSAS), which is characterized by mental retardation and enlarged brain ventricles, maps to the same subchromosomal region (Xq28) as the gene for neural cell adhesion molecule L1 [8].
• Reduced reactivity to novelty, impaired social behavior, and enhanced basal synaptic excitatory activity in perforant path projections to the dentate gyrus in young adult mice deficient in the neural cell adhesion molecule CHL1 [9].
• Antibodies or fragments that bind to the extracellular domains of NCAM or Ll at this time produce amnesia for the task [10].

High impact information on NCAM1

• We have determined the crystal structure of the ligand binding fragment of the neural cell adhesion molecule axonin-1/TAG-1 comprising the first four immunoglobulin (Ig) domains [11].
• We have previously shown that X-linked hydrocephalus is caused by mutations in the gene for neural cell adhesion molecule L1 (L1CAM), an axonal glycoprotein involved in neuronal migration and differentiation [12].
• Aberrant splicing of neural cell adhesion molecule L1 mRNA in a family with X-linked hydrocephalus [8].
• Here the structure of a novel secreted isoform of N-CAM is established by analysis of a cDNA corresponding to an N-CAM mRNA from human skeletal muscle [13].
• Alternative splicing generates a secreted form of N-CAM in muscle and brain [13].

Chemical compound and disease context of NCAM1

• Neuroprotection mediated by subtoxic dose of NMDA in SH-SY5Y neuroblastoma cultures: activity-dependent regulation of PSA-NCAM expression [14].
• By combining intranuclear bromodeoxyuridine (BrdU) staining and analysis of CD56 marker intensity, statistically higher percentages of BrdU(+) cells were found among the CD56(bright) subset than the CD56(dim) subset after 6 days of stimulation with BCG [15].
• Up to now, no systematic analysis of the expression pattern of CD56 in formalin fixed paraffin embedded bone marrow biopsies of acute leukemias has been performed [16].
• We immunohistochemically studied the expression of CD56 in a series of 141 bone marrow biopsies fixed in Sublimat Mercury II Chloride (SUSA) including 100 cases of AML FAB M0-M7, 11 cases of AML not further specified, 3 cases of biphenotypical leukemia, 20 cases of acute lymphoblastic leukemia (ALL) and 7 cases of reactive bone marrow biopsies [16].
• Similar CD56+ luminal cell clusters were also observed in cases of chronic pancreatitis, whereas they were scarce in normal adult and diabetic tissues [17].

Biological context of NCAM1

• Neural cell adhesion molecule 1 (NCAM1) is known to play important roles in cell migration, neurite growth, axonal guidance, and synaptic plasticity [6].
• TPARM gene, located between NCAM1 and DRD2 genes, was mapped to human chromosome 11q23 [1].
• Polysialic acid is a developmentally regulated posttranslational modification of the neural cell adhesion molecule (N-CAM) [18].
• For this expression cloning, COS-1 cells were cotransfected with a human fetal brain cDNA library and a cDNA encoding human N-CAM [18].
• These results suggest that the glycosylation of each N-CAM isoform might be regulated independently [19].

Anatomical context of NCAM1

• This is the first demonstration of the production of N-CAM glycoforms carrying different oligosaccharides by a homogeneous astrocyte preparation [19].
• Gangliogenesis in the enteric nervous system: Roles of the polysialylation of the neural cell adhesion molecule and its regulation by bone morphogenetic protein-4 [20].
• Therefore, we were prompted to examine if CD56 molecules on NK cells interact with FGFR expressed on T cells [21].
• While it is known that CD56 is a molecular isoform of NCAM expressed on human NK cells and a subset of T cells, it remains poorly characterized, with its ligand unidentified [21].
• Costimulation of T cell receptor-triggered IL-2 production by Jurkat T cells via fibroblast growth factor receptor 1 upon its engagement by CD56 [21].

Associations of NCAM1 with chemical compounds

• Polysialic acid (PSA) is a carbohydrate composed of a linear homopolymer of alpha-2-8-linked sialic acid residues and is mainly attached to the neural cell adhesion molecule (NCAM) [2].
• We first examined whether PST and STX differ in the requirement of sialic acid and core structures of N-glycans attached to NCAM [22].
• Polysialic acid is a developmentally regulated, anti-adhesive glycan that is added to the neural cell adhesion molecule, NCAM [23].
• Therefore, the single enzyme, ST8Sia II, directly transferred all alpha2,8-sialic acid residues on the alpha2,3-linked sialic acids of N-glycans of specific NCAM isoforms to yield PSA-NCAM [24].
• Molecular dissection of the ST8Sia IV polysialyltransferase. Distinct domains are required for neural cell adhesion molecule recognition and polysialylation [25].
• Replacing Arg(82)/Arg(93) in ST8Sia IV with alanine substantially decreased NCAM-specific polysialylation while only partially impacting autopolysialylation, suggesting that these residues may be particularly important for NCAM polysialylation [26].

Physical interactions of NCAM1

• Furthermore, ST8Sia IV was able to add polysialic acid to oligosialylated oligosaccharides and unpolysialylated antennas in N-glycans attached to NCAM, even when polysialic acid was attached to at least one of the other antennas [27].
• GFRalpha1 lacking its N-terminal domain was still able to potentiate GDNF binding to NCAM and assemble into a tripartite receptor complex but showed a reduced capacity to attenuate NCAM-mediated cell adhesion [28].

Enzymatic interactions of NCAM1

• The MAP kinase activation was sustained, because ERK1 and ERK2 were phosphorylated in PC12-E2 cells and primary hippocampal neurons even after 24 hr of cultivation on NCAM-expressing fibroblasts [29].
• We examined normal and Huntington's disease (HD) human striatum with specific monoclonal antibodies to nonphosphorylated (SMI 32) and phosphorylated (SMI 31) neurofilament and neural cell adhesion molecule (NCAM) [30].

Regulatory relationships of NCAM1

• BMP-4 promoted neuronal NCAM polysialylation and clustering [20].
• A 15-amino-acid long peptide, the FG loop (FGL) peptide, that is derived from the second F3 module of NCAM has been found to activate FGFR1 [31].
• CD34 antigen was co-expressed in 3 of the 4 patients with CD56+ APL, in contrast to 2 of the 24 patients with CD56- APL (P = .01) [32].
• The transfected Lec2-NCAM cells expressing the HNK-1 glycan were enriched by fluorescence-activated cell sorting [33].
• Neural cell adhesion molecule (NCAM) induces neuronal phenotype acquisition in dominant negative MEK1-expressing hippocampal neural progenitor cells [34].

Other interactions of NCAM1

• These results indicate that the cloned polysialyltransferase forms polysialylated, embryonic N-CAM, which is critical for plasticity of neural cells [18].
• Previous studies indicate that ST8Sia IV forms more highly polysialylated N-glycans on NCAM than ST8Sia II in vitro [27].
• A Novel {alpha}-Helix in the First Fibronectin Type III Repeat of the Neural Cell Adhesion Molecule Is Critical for N-Glycan Polysialylation [23].
• First, we found that ST8Sia III can form polysialic acid on the enzyme itself (autopolysialylation) but not on NCAM [35].
• Furthermore, N-CAM 180 did not carry the HNK-1 epitope, whereas the other two isoforms did [19].

Analytical, diagnostic and therapeutic context of NCAM1

• Both fractions thus obtained were subjected to immunoblotting using an anti-N-CAM monoclonal antibody [19].
• These findings suggest that ligation of FGFR1 by CD56 may contribute to the interaction between NK cells and T cells that we have postulated in our previous studies [21].
• This was done using a coculture system consisting of PC12-E2 cells grown on fibroblasts, with or without NCAM expression, allowing NCAM-NCAM interactions resulting in neurite outgrowth [29].
• NCAM was measured in the sera of 70 control subjects and 43 DAT patients (with different severity of cognitive impairment, GDS), employing Western blot and densitometric quantification [7].
• Immunoprecipitation of a panel of SCLC cell lines by monoclonal antibodies (mAbs) specific for N-CAM detects mainly the 145-kDa isoform [36].

References