Disease relevance of CNTN2

• A homologue of the axonally secreted protein axonin-1 is an integral membrane protein of nerve fiber tracts involved in neurite fasciculation [1].
• Axonin-1 was expressed in amacrine cells from E8 onward in the inner nuclear, in the inner plexiform, and in the ganglion cell layer [2].
• AdCMVax-1 harbours the entire coding region of the chicken axonin-1 cDNA under the transcriptional control of the Cytomegalovirus enhancer/promoter in the early-region 1 of the viral genome [3].

High impact information on CNTN2

• This arrangement suggests that cell adhesion by homophilic axonin-1 interaction occurs by the formation of a linear zipper-like array in which the axonin-1 molecules are alternately provided by the two apposed membranes [4].
• Whereas nociceptive pathfinding depends on NgCAM and axonin-1, proprioceptive fibers require NrCAM and F11 [5].
• Using an in vivo approach, we demonstrate an involvement of the two immunoglobulin superfamily cell adhesion molecules axonin-1/TAG-1 and F11/F3/contactin in subpopulation-specific sensory axon guidance [5].
• Distinct subpopulations of sensory afferents require F11 or axonin-1 for growth to their target layers within the spinal cord of the chick [5].
• The present in vivo study demonstrates that interactions by two of these molecules, axonin-1 on commissural growth cones and Nr-CAM on floor plate cells, are required for accurate pathfinding at the midline [6].

Biological context of CNTN2

• Tissue-specific expression of the axonin-1 gene seems to be regulated in part by sequences more than 1 kb upstream of the transcription initiation site [7].
• Each of the six immunoglobulin-like domains and the four fibronectin-type-III-like domains of axonin-1 is encoded by two exons [7].
• Control embryos electroporated with vehicle, or with dsRNA targeting choline acetyltransferase or axonin-1, did not exhibit this phenotype [8].

Anatomical context of CNTN2

• By antibody blockage experiments an axonin-1 receptor on the glial cells was identified as Nr-CAM [9].
• Together, these results implicate a binding between axonin-1 of the neuritic and Nr-CAM of the glial cell membrane in the early phase of axon ensheathment in the peripheral nervous system [9].
• Nr-CAM promotes neurite outgrowth from peripheral ganglia by a mechanism involving axonin-1 as a neuronal receptor [10].
• Axonin-1 is an axon-associated cell adhesion molecule (AxCAM) of the chicken, which promotes neurite outgrowth by interaction with the AxCAM L1(G4) of the neuritic membrane [11].
• Using selective metabolic labelling in a compartmental cell culture system two proteins, denoted axonin-1 and axonin-2, were found to be secreted by axons of dorsal root ganglia neurons from chicken embryos [12].

Associations of CNTN2 with chemical compounds

• In search for novel ligands of axonin-1, fluorescent polystyrene microspheres conjugated with axonin-1 were found to bind to peripheral glial cells from dorsal root ganglia [9].
• Axonin-1 is a glycoprotein that is released from axons of cultured neurons (Stoeckli, E. T., P. F. Lemkin, T. B. Kuhn, M. A. Ruegg, M. Heller, and P. Sonderegger. 1989. Eur. J. Biochem. 180:249-258) [1].
• These effects of L-serine were found to be concentration-dependent and stereospecific and were observed on several different substrata such as laminin, Ng-CAM and axonin-1 [13].

Other interactions of CNTN2

• Homology modeling using axonin-1 as a template reveals that the four aminoterminal Ig domains of FAR-2 form a compact U-shaped structure, which is likely to contain functionally important ligand-binding sites [14].
• The axonally secreted cell adhesion molecule, axonin-1. Primary structure, immunoglobulin-like and fibronectin-type-III-like domains and glycosyl-phosphatidylinositol anchorage [11].
• Double or triple labelling studies for LHRH, somatostatin and/or axonin-1 showed that LHRH neurons entered the spinal nerve in contact with the olfactory axons, which are specifically immunoreactive to somatostatin [15].
• A newly-synthesized GPI-anchored protein, TAG-1/axonin-1, is inserted into axonal membranes along the entire length of the axon and not exclusively at the growth cone [16].

Analytical, diagnostic and therapeutic context of CNTN2

• Here we report the cloning and sequence determination of a cDNA encoding axonin-1 [11].
• Degenerated polymerase chain reaction (PCR) primers were designed and an axonin-1 fragment was amplified from mRNA of embryonic retina [11].
• Based on its characteristic coordinates and spot morphology in two-dimensional gel electrophoresis, axonin-1 was detected in the cerebrospinal fluid and the vitreous fluid, axonin-1 was purified 476-fold to homogeneity by a four-step chromatographic procedure [12].
• Immunohistochemistry localized axonin-1 prevalently in developing nerve fiber tracts [1].
• To help understand how axons interact as they grow into the developing chick hindlimb, we used electron microscopy in conjunction with immunoperoxidase staining for the cell adhesion molecule axonin-1 to label sensory axons [17].

References