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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neural cell adhesion molecule (NCAM), probably the best characterized and most abundant cell adhesion molecule on neurons, is thought to be a major regulator of axonal growth and pathfinding. Here we present a detailed analysis of these processes in mice deficient for all NCAM isoforms, generated by gene targeting. The hippocampal mossy fiber tract shows prominent expression of polysialylated NCAM and the generation of new axonal projections throughout life. Focusing on this important intrahippocampal connection, we demonstrate that in the absence of NCAM, fasciculation and pathfinding of these axons are strongly affected. In addition we show alterations in the distribution of mossy fiber terminals. The phenotype is more severe in adult than in young animals, suggesting an essential role for NCAM in the maintenance of plasticity in the mature nervous system.
Mol Cell Neurosci 1997
PMID:NCAM is essential for axonal growth and fasciculation in the hippocampus. 907 95

E587 antigen, an L1-related cell adhesion molecule, is expressed by growing axons and has previously been shown to enhance axon growth and to mediate fasciculation of axons from newborn retinal ganglion cells in goldfish. In zebrafish, the monoclonal antibody E17 against E587 antigen stains all axons in the primary tracts and commissures from 17 h postfertilization (pf) onward and axons which are added subsequently to this scaffold. Moreover, Fab fragments of an E587 antiserum (E587 Fabs) injected into the ventricle of 30-h pf zebrafish embryos caused a marked defasciculation of distinct axon bundles in the posterior commissure, in hindbrain commissures, and in longitudinal tracts of the hindbrain, where they also caused increased crossings between fascicles. The regulated expression of E587 antigen by all developing axons and the effects caused by E587 Fabs show that E587 antigen contributes to the formation of tight and orderly fascicles in the developing CNS.
Mol Cell Neurosci 1997 Jan
PMID:Expression of an L1-related cell adhesion molecule on developing CNS fiber tracts in zebrafish and its functional contribution to axon fasciculation. 920 81

F3 is a developmentally regulated adhesive glycoprotein expressed by subpopulations of central and peripheral neurons which mediates neurite growth and fasciculation via cis- and trans-interactions with cell-surface or matrix components. We previously reported on the characterization of the F3 gene 5' flanking region in which we identified promoter and enhancer elements. Here, we report on the functional organization of the F3 gene regulatory regions. We show that the F3 promoter is built of linearly arranged positive and negative elements scattered through the 5' flanking region of the F3 gene and the 1st exon (exon 0). Neural- and cell type-specific expression of F3 appears to be governed by elements located in the most proximal promoter region which includes a neural-specific enhancer. In retardation assays, all these cis-acting elements bind nuclear proteins, three of which interact with the identified enhancer element while a single species interacts with sequences located within exon 0. Some of these proteins are also specifically expressed within the brain, indicating that they could correspond to neural-specific trans-acting factors. Elements located immediately upstream of the cell type-specific enhancer and within exon 0 are responsible for regulation of F3 expression by cAMP and retinoic acid.
Brain Res Mol Brain Res 1997 Sep
PMID:Functional organization of the promoter region of the mouse F3 axonal glycoprotein gene. 933 25

Motor neurone disease is a rapidly progressive neurodegenerative disorder, characterized by muscular weakness and wasting with fasciculation and by spasticity. While most cases are sporadic, approximately 10% are inherited in an autosomal dominant mode. Recently, mutations in the gene encoding the free-radical scavenging enzyme superoxide dismutase-1 have been found to segregate with the disorder in 20% of familial cases. This is an exciting development, as free radical damage has long been implicated in the pathogenesis of motor neurone disease and it raises the possibility of novel therapeutic approaches in this otherwise fatal condition.
Mol Med Today 1995 Jul
PMID:Mechanisms in motor neurone disease: clues from genetic studies. 941 57

Previous studies have shown that brain derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) can enhance the survival of dopaminergic neurons in the ventral mesencephalon (VM). Here we compared several non-survival functions of the two factors in VM neurons in culture. We found that both BDNF and GDNF elicited an increase in the depolarization-induced release of dopamine, but had no effect on GABA release, in the VM cultures. BDNF, but not GDNF, significantly enhanced the expression of the calcium binding protein calbindin and synaptic protein SNAP25. In contrast, treatment of the cultures with GDNF, but not BDNF, elicited a marked fasciculation of the processes of the VM neurons. Thus, although both act on VM neurons, BDNF and GDNF have distinct functions.
Brain Res Mol Brain Res 1999 Mar 20
PMID:Differential effects of GDNF and BDNF on cultured ventral mesencephalic neurons. 1009 78

Morphological alterations in the brains of schizophrenia patients suggest that neurodevelopmental dysfunction is involved in the etiology of the disease.(1) Such dysfunction may be due to functional alterations of cell adhesion molecules, which play important roles in cell migration, axonal growth, fasciculation, synaptogenesis, and synaptic remodeling. We screened for mutations in the coding region of the close homologue to L1 gene (CHL1), which is located on human chromosome 3p26, in 24 Japanese patients with schizophrenia. A missense polymorphism (Leu17Phe) in the signal peptide region was identified. A case-control comparison revealed significantly higher frequencies of the Leu/Leu genotype (P = 0.004) and the Leu allele (P = 0.006) in 282 Japanese schizophrenic patients than in 229 Japanese control subjects. The estimated odds ratio for schizophrenia was 1.83 (95% CI, 1.28-2.26) for the Leu/Leu genotype compared with the other genotypes. An association between this CHL1 gene polymorphism and schizophrenia supports the notion that cell adhesion molecules are involved in the etiology of schizophrenia.
Mol Psychiatry 2002
PMID:An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia. 1198 85

The neural cell adhesion molecule L1 plays important roles in cell adhesion, neuronal migration, neurite outgrowth, fasciculation and pathfinding, neuronal survival, and synaptic plasticity. Many of these functions have been identified and characterized by using antibodies. Because of the need for reproducible and functionally active antibodies, we have generated two single-chain variable fragment antibodies against mouse L1 from a human synthetic phage display library. The complementarity determining region 3 of the variable heavy chains of the two antibodies differed in length and sequence. Both antibodies recognized mouse, but not human L1, by enzyme-linked immunosorbent assay, Western blot, and immunofluorescence staining of cultured neurons. Epitope mapping showed reactivity with the fibronectin type III repeats 1-2 of mouse L1. The antibodies stimulated neurite outgrowth from cerebellar dorsal, root ganglion and motor neurons when offered in substrate-coated form in a dose-dependent manner with maximal effects at approximately 32 nM. Furthermore, substrate-coated antibodies enhanced survival of cerebellar neurons. Peptides comprising 8 and 11 amino acids derived from the complementarity determining region 3 of the variable heavy chains of the two single-chain variable fragment antibodies also promoted neurite outgrowth. The combined observations indicate that single-chain variable fragment antibodies against L1 and peptides derived from their binding domains can mimic some beneficial functions of homophilically binding L1 in vitro and may thus serve to trigger these functions in vivo.
Mol Cell Neurosci 2003 Feb
PMID:Single chain Fv antibodies against neural cell adhesion molecule L1 trigger L1 functions in cultured neurons. 1267 33

Disrupted-In-Schizophrenia 1 (DISC1) was identified as a novel gene disrupted by a (1;11)(q42.1;q14.3) translocation that segregated with schizophrenia in a Scottish family. Predicted DISC1 product has no significant homology to other known proteins. Here, we demonstrated the existence of DISC1 protein and identified fasciculation and elongation protein zeta-1 (FEZ1) as an interacting partner of DISC1 by a yeast two-hybrid study. FEZ1 and its nematode homolog are reported to represent a new protein family involved in axonal outgrowth and fasciculation. In cultured hippocampal neurons, DISC1 and FEZ1 colocalized in growth cones. Interactions of these proteins were associated with F-actin. In the course of neuronal differentiation of PC12 cells, upregulation of DISC1/FEZ1 interaction was observed as along with enhanced extension of neurites by overexpression of DISC1. The present study shows that DISC1 participates in neurite outgrowth through its interaction with FEZ1. Recent studies have provided reliable evidence that schizophrenia is a neurodevelopmental disorder. As there is a high level of DISC1 expression in developing rat brain, dysfunction of DISC1 may confer susceptibility to psychiatric illnesses through abnormal development of the nervous system.
Mol Psychiatry 2003 Jul
PMID:Disrupted-In-Schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth. 1287 5

Cell adhesion molecules (CAMs) of the immunoglobulin superfamily (IgSF) exhibit restricted spatial and temporal expression profiles requiring a tight regulatory program during development. The rodent glycoprotein TAG-1 and its orthologs TAX-1 in the human and axonin-1 in chick are cell adhesion molecules belonging to the contactin/F3 subgroup of the IgSF. TAG-1 is expressed in restricted subsets of central and peripheral neurons, not only during development but also in adulthood, and is implicated in neurite outgrowth, axon guidance and fasciculation, as well as neuronal migration. In an attempt to identify the regulatory elements that guide the neuronal expression of TAG-1, we have isolated genomic clones containing 4 kb of the TAX-1 upstream sequence and used them to drive the expression of the LacZ reporter gene in transgenic mice. We demonstrate that this sequence includes elements not only sufficient to restrict expression to the nervous system, but also to recapitulate to a great extent the endogenous pattern of the TAG-1 expression in the developing CNS.
Brain Res Mol Brain Res 2003 Oct 21
PMID:The upstream regulatory region of the gene for the human homologue of the adhesion molecule TAG-1 contains elements driving neural specific expression in vivo. 1455 58

Neural cell adhesion molecules (CAMs) are important players during neurogenesis and neurite outgrowth as well as axonal fasciculation and pathfinding. Some of these developmental processes entail the activation of cellular signaling cascades. Pharmacological and genetic evidence indicates that the neurite outgrowth-promoting activity of L1-type CAMs is at least in part mediated by the stimulation of neuronal receptor tyrosine kinases (RTKs), especially FGF and EGF receptors. It has long been suspected that neural CAMs might physically interact with RTKs, but their activation by specific cell adhesion events has not been directly demonstrated. Here we report that gain-of-function conditions of the Drosophila L1-type CAM Neuroglian result in profound sensory axon pathfinding defects in the developing Drosophila wing. This phenotype can be suppressed by decreasing the normal gene dosage of the Drosophila EGF receptor gene. Furthermore, in Drosophila S2 cells, cell adhesion mediated by human L1-CAM results in the specific activation of human EGF tyrosine kinase at cell contact sites and EGF receptors engage in a physical interaction with L1-CAM molecules. Thus L1-type CAMs are able to promote the adhesion-dependent activation of EGF receptor signaling in vitro and in vivo.
Mol Biol Cell 2004 Apr
PMID:Activation of EGF receptor kinase by L1-mediated homophilic cell interactions. 1471 70


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