title: Neurite outgrowth on immobilized axonin-1 is mediated by a heterophilic interaction with L1(G4).
abstract: Axonin-1 is an axon-associated cell adhesion molecule with dualistic expression, one form being glycophosphatidylinositol-anchored to the axonal membrane, the other secreted from axons in a soluble form. When presented as a substratum for neuronal cultures it strongly promotes neurite outgrowth from chicken embryonic dorsal root ganglia neurons. In this study, the axon-associated cell adhesion molecule G4, which is identical with Ng-CAM and 8D9, and homologous or closely related to L1 of the mouse and NILE of the rat, was investigated with respect to a receptor function for axonin-1. Using fluorescent microspheres with covalently coupled axonin-1 or L1(G4) at their surface we showed that these proteins bind to each other. Within the sensitivity of this microsphere assay, no interaction of axonin-1 with itself could be detected. Axonin-1-coated microspheres also bound to the neurites of cultured dorsal root ganglia neurons. This interaction was exclusively mediated by L1(G4), as indicated by complete binding suppression by monovalent anti-L1(G4) antibodies. The interaction between neuritic L1(G4) and immobilized axonin-1 was found to mediate the promotion of neurite growth on axonin-1, as evidenced by the virtually complete arrest of neurite outgrowth in the presence of anti-L1(G4) antibodies. Convincing evidence has recently been presented that neurite growth on L1(8D9) is mediated by the homophilic binding of neuritic L1(G4) (1989. Neuron. 2: 1597-1603). Thus, both L1(G4)- and axonin-1-expressing axons may serve as "substrate pathways" for the guidance of following axons expressing L1(G4) into their target area. Conceivably, differences in the concentration of axonin-1 and L1(G4), and/or modulatory influences on their specific binding parameters in leading pathways and following axons could represent elements in the control of axonal pathway selection.
authors.affiliation: Institute of Biochemistry, University of Zurich, Switzerland.
authors.forename: T B
authors.initials: TB
authors.lastname: Kuhn
authors.forename: E T
authors.initials: ET
authors.lastname: Stoeckli
authors.forename: M A
authors.initials: MA
authors.lastname: Condrau
authors.forename: F G
authors.initials: FG
authors.lastname: Rathjen
authors.forename: P
authors.initials: P
authors.lastname: Sonderegger
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D002642:Chick Embryo; D058969:Contactin 2; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008863:Microspheres; D016501:Neurites / Q000378:metabolism*; D019063:Tenascin
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C548675:Cntn2 protein, mouse; C548676:Cntn2 protein, rat; D058969:Contactin 2; D016326:Extracellular Matrix Proteins; D019063:Tenascin