title: Cell-cell adhesion by homophilic interaction of the neuronal recognition molecule axonin-1.
abstract: The axonal surface glycoprotein axonin-1, which occurs both as a glycosyl-phosphatidylinositol-anchored membrane-bound form and a secreted form, promotes neurite outgrowth and is thought to be involved in axon-guidance mechanisms in the developing nervous system. Recently, we have demonstrated that the neurite-outgrowth-promoting activity of axonin-1, presented as a substratum for cultured neurons, is mediated by a heterophilic interaction with the axonal glycoprotein neuronglia cell-adhesion molecule (Ng-CAM). Here we present evidence for homophilic (like-like) binding among axonin-1 molecules. Axonin-1 was heterologously expressed in myeloma cells. Clonal cell lines, with exposed membrane-bound axonin-1 at their surface, formed large multicellular aggregates. Incubations of transfected and parental myeloma cells, under a series of different conditions, revealed homophilic axonin-1/axonin-1 interactions across the intermembrane space as the molecular mechanism promoting stable cell-cell contacts. Using structural and functional characterisation, recombinant axonin-1 was very similar to native axonin-1, suggesting that homophilic axonin-1 interactions are also established in neurons. The capability of axonin-1 to interact with both Ng-CAM and other axonin-1 molecules might contribute to the formation of macromolecular networks at contact sites of growth cones and axons, comprising molecules of both membranes, and thus represent a mechanism for regulating neurite outgrowth and pathfinding.
authors.affiliation: Institute of Biochemistry, University of Zurich, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Rader
authors.forename: E T
authors.initials: ET
authors.lastname: Stoeckli
authors.forename: U
authors.initials: U
authors.lastname: Ziegler
authors.forename: T
authors.initials: T
authors.lastname: Osterwalder
authors.forename: B
authors.initials: B
authors.lastname: Kunz
authors.forename: P
authors.initials: P
authors.lastname: Sonderegger
mesh_terms: D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002449:Cell Aggregation; D002450:Cell Communication; D002642:Chick Embryo; D058969:Contactin 2; D006801:Humans; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000032:analysis; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: C548674:CNTN2 protein, human; D015816:Cell Adhesion Molecules, Neuronal; D058969:Contactin 2; D011994:Recombinant Proteins