Disease relevance of Cntn1

• We examined the expression and function of sodium channels in small-diameter dorsal root ganglion (DRG) neurons from contactin-deficient (CNTN-/-) mice, compared to CNTN+/+ litter mates [1].
• Contactin, a cell adhesion/recognition molecule of the immunoglobulin gene superfamily, regulates axon growth and fasciculation in vitro, but its role in vivo is unknown [2].

High impact information on Cntn1

• The contactin mutation does not affect sodium channel clustering at the nodes of Ranvier but alters the location of the Shaker-type Kv1.1 and Kv1.2 potassium channels [3].
• Contactin orchestrates assembly of the septate-like junctions at the paranode in myelinated peripheral nerve [3].
• Ablation of contactin in mutant mice disrupts junctional attachment at the paranode and reduces nerve conduction velocity 3-fold [3].
• To assess its function in the developing nervous system, we have ablated contactin gene expression in mice [2].
• These results demonstrate that contactin controls axonal and dendritic interactions of cerebellar interneurons and contributes to cerebellar microorganization [2].

Biological context of Cntn1

• The cell adhesion molecules caspr/paranodin and F3/contactin play a crucial role in the generation of functional septate-like junctions at paranodes [4].
• The F3 nucleotide and deduced amino acid sequence show striking similarity to the recently published sequence of the chicken neuronal cell surface protein contactin [5].
• A mutation in the Contactin-1 gene results in an ataxic and anorectic phenotype that is apparent by postnatal day 10 and lethal by postnatal day 19 [Berglund et al. (1999) Neuron 24, 739-750] [6].
• The resemblance of this phenotype with the anorexia (anx/anx) mouse mutation prompted us to investigate the hypothalamic neurochemistry of Contactin knock-out (KO) mice [6].
• The data indicate that differential regulation of the F3/Contactin expression during development may depend upon alternative utilization of distinct promoter elements and may involve complex splicing events of the 5' untranslated exons [7].

Anatomical context of Cntn1

• Whereas contactin is insoluble in nonionic detergent and is tightly associated with the cytoskeleton, about equal amounts of F3 distribute between buffer-soluble, nonionic detergent-soluble, and detergent-insoluble fractions [5].
• Clustering of contactin on the cell surface induced coclustering of Caspr and immobilized protein 4.1B at the plasma membrane [8].
• Alterations of arcuate nucleus neuropeptidergic development in contactin-deficient mice: comparison with anorexia and food-deprived mice [6].
• Contactin was expressed in the hypothalamic neuropil of wild-type (WT) but not Contactin KO mice [6].
• These changes in the pattern of neuropeptide expression in the Contactin-deficient hypothalamus were similar but more pronounced than those found in anx/anx mice [6].

Associations of Cntn1 with chemical compounds

• Contactin selectively supports paired-pulse facilitation (PPF) and NMDA (N-methyl-D-aspartate) receptor-dependent LTD but is not required for synaptic morphology, basal transmission, or LTP [9].
• Cell surface transport of F3/contactin and caspr/paranodin is insensitive to brefeldin A and the two glycoproteins are endoglycosidase H-sensitive when associated in complex, recruited into the lipid rafts, and expressed on the cell surface [4].
• Alternative promoters drive the expression of the gene encoding the mouse axonal glycoprotein F3/contactin [7].
• CS-E, but not CS-A, -C, or heparan sulfate, engaged CNTN-1 with significant affinity and induced intracellular signaling downstream of CNTN-1, indicating that CS-E is a selective ligand for a potential CS receptor, CNTN-1, leading to neurite outgrowth [10].

Physical interactions of Cntn1

• These results suggest that Caspr serves as a "transmembrane scaffold" that stabilizes the Caspr/contactin adhesion complex at the paranodal junction by connecting it to cytoskeletal components within the axon [8].
• F3/Contactin is a neuronal glycoprotein which mediates axonal growth control via complex interactions with a number of cell surface or matrix components [7].

Other interactions of Cntn1

• Engagement of the contactin-Caspr complex with RPTPbeta may thus regulate cell-cell interactions contributing to specific synaptic plasticity forms [9].
• Using whole-cell patch-clamp recording, we observed a greater than two-fold reduction of tetrodotoxin-resistant (TTX-R) Nav1.8 and Nav1.9 current densities in IB4+ DRG neurons cultured from CNTN-/- vs. CNTN+/+ mice [1].
• Synaptotagmin 1 and contactin 1 were eliminated as candidate genes for the med mutation [11].
• Transgenic mice expressing F3/contactin from the transient axonal glycoprotein promoter undergo developmentally regulated deficits of the cerebellar function [12].
• Expression and regulation of a gene encoding neural recognition molecule NB-3 of the contactin/F3 subgroup in mouse brain [13].

Analytical, diagnostic and therapeutic context of Cntn1

• Contactin mRNA expression was characterized using Northern blot analyses of human tissues and cell lines [14].

References