Disease relevance of CNTN1

• The gene for contactin-1 was found to play an essential role in tumor invasion and metastasis [1].
• Knockdown of contactin-1 expression suppresses invasion and metastasis of lung adenocarcinoma [1].
• Our findings suggest that contactin has repellent effects on glioma cells to which it is presented as a ligand, but it does not alter the proliferative or adhesive capacities of cells that overexpress the molecule [2].
• Using subtractive cloning, we identified contactin transcripts as overexpressed in glioblastomas compared with normal brain [2].
• Contactin is expressed in human astrocytic gliomas and mediates repulsive effects [2].

High impact information on CNTN1

• F3/Notch signaling promotes oligodendrocyte precursor cell differentiation and upregulates the myelin-related protein MAG in OLN-93 cells [3].
• We report Nogo-A as an oligodendroglial component congregating and interacting with the Caspr-F3 complex at paranodes [4].
• Cotransfection with F3 resulted in plasma membrane delivery of paranodin, as analyzed by confocal microscopy and cell surface biotinylation [5].
• The association of paranodin with F3 allowed its recruitment to Triton X-100-insoluble microdomains [5].
• PTPalpha and contactin associate in a lateral (cis) complex mediated through the extracellular region of PTPalpha [6].

Chemical compound and disease context of CNTN1

• Overexpression of contactin by transfection into glioblastoma cells did not alter the proliferation rate or adhesion to various extracellular matrix proteins as well as adhesion to cells expressing the specific contactin ligand the protein tyrosine phosphatase zeta (PTPzeta) [2].
• Here we describe a consistent and significant sequence-similarity between the ovine/caprine lentivirus surface glycoprotein gp135 and the primate lentivirus gp120 in the region between variable loops V2 and V3 [7].

Biological context of CNTN1

• Molecular cloning and in situ localization of the human contactin gene (CNTN1) on chromosome 12q11-q12 [8].
• These animals (TAG/F3 mice) display a developmentally regulated cerebellar phenotype in which the size of the cerebellum is markedly reduced during the first two postnatal weeks but subsequently recovers [9].
• Antibodies to the cell adhesion molecule F3/contactin of the Ig superfamily blocked the BD- but not the D6-dependent effect [10].
• The alternatively spliced BD cassettes are prominently expressed in the developing hippocampus, as shown by reverse transcription PCR, and colocalize with F3 expression during perinatal periods when axon growth and the establishment of hippocampal connections take place [10].
• Many of them, including the drosophila fasciclin 1 as well as the mammalian glycoproteins Thy-1, TAG1, N-CAM and F11,F3, contactin are members of the immunoglobulin gene superfamily [11].

Anatomical context of CNTN1

• These data are consistent with a model in which deployment of F3/contactin on granule cells affects proliferation and differentiation of these neurons as well as the differentiation of their synaptic partners, the Purkinje cells [9].
• We showed previously that a recombinant Fc fusion protein with the C domain (beta C) binds to contactin and supports neuronal adhesion and neurite growth [12].
• Contactin-1 was differentially expressed in tumor tissues, and its expression correlated with tumor stage, lymph node metastasis, and patient survival [1].
• Suppression of contactin-1 expression abolished the ability of lung adenocarcinoma cells to invade Matrigel in vitro as well as the polymerization of filamentous-actin and the formation of focal adhesion structures [1].
• In contrast, normal astrocytes did not express contactin [2].

Associations of CNTN1 with chemical compounds

• Induction of neurite outgrowth through contactin and Nr-CAM by extracellular regions of glial receptor tyrosine phosphatase beta [12].
• Through affinity chromatography of membrane glycoproteins from chick brain on tenascin-Sepharose, we isolated a major cell surface ligand of 135 kD which we identified as contactin/F11 by NH2-terminal sequencing [13].
• Regulated expression of the cell adhesion glycoprotein F3 in adult hypothalamic magnocellular neurons [14].
• Confocal and electron microscopy localized F3 in secretory granules in all neuronal compartments, a localization confirmed by detection of F3 immunoreactivity in granule-enriched fractions obtained by sucrose density gradient fractionation of rat neurohypophyses [14].
• In the present study, we report the isolation of two fractions of F3-containing microdomains from adult cerebellum on the basis of their resistance to solubilization by Triton X-100 at 4 degrees C. Both fractions were composed of vesicles, ranging from 100 to 200 nm in diameter [15].

Physical interactions of CNTN1

• These results suggest that binding of glial RPTPbeta to the contactin/Nr-CAM complex is important for neurite growth and neuronal differentiation [12].
• Previously, we have demonstrated that TN-R induces microprocesses along neurites and enlarged growth cones of tectal cells by interacting with the cell adhesion molecule contactin 1 [16].

Other interactions of CNTN1

• NB-2 is one of the neural recognition molecules in the contactin subgroup, which belongs to the immunoglobulin superfamily [17].
• We confirmed contactin overexpression in glioblastomas at the protein level, and localized contactin to the surface of glial fibrillary acidic protein (GFAP)-expressing glioblastoma cells [2].
• In sciatic nerve, the expression of contactin, receptor protein tyrosine phosphatase beta, and the Na(+)-channel beta(1) subunit, paranodal caspr and nodal ankyrin(G) was unaltered in 2-month type 1 diabetic BB/Wor rats but significantly decreased after 8 months of diabetes [18].
• Here, we describe competition and cooperation between TN-R, lecticans and contactin 1, and their functional consequences for tectal cells [16].
• The binding specificity between contactin/F11 and tenascin was demonstrated in solid-phase assays [13].

Analytical, diagnostic and therapeutic context of CNTN1

• Furthermore, knockdown of contactin-1 resulted in extensive inhibition of tumor metastasis and in increased survival in an animal model [1].
• Accordingly, deletion of Caspr in mice by gene targeting results in a shift from the LMw- to a HMw-contactin glycoform [19].
• In situ hybridization revealed that F3 expression in the hypothalamus is restricted to its magnocellular neurons and demonstrated a more than threefold increase in F3 mRNA levels in response to stimulation [14].
• Immunoprecipitation experiments indicated that F3, but not NCAM 120 or Thy-1, was physically associated in a complex with both L1 and fyn tyrosine kinase [15].
• As seen from immunocytochemistry of live cells and immunoblot analysis, treatment of cultures with a GPI-specific phospholipase C (GPI-PLC) resulted in loss of F3/contactin immunoreactivity from all cell surfaces [20].

References