title: Neurite fasciculation mediated by complexes of axonin-1 and Ng cell adhesion molecule.
abstract: Neural cell adhesion molecules composed of immunoglobulin and fibronectin type III-like domains have been implicated in cell adhesion, neurite outgrowth, and fasciculation. Axonin-1 and Ng cell adhesion molecule (NgCAM), two molecules with predominantly axonal expression exhibit homophilic interactions across the extracellular space (axonin- 1/axonin-1 and NgCAM/NgCAM) and a heterophilic interaction (axonin-1-NgCAM) that occurs exclusively in the plane of the same membrane (cis-interaction). Using domain deletion mutants we localized the NgCAM homophilic binding in the Ig domains 1-4 whereas heterophilic binding to axonin-1 was localized in the Ig domains 2-4 and the third FnIII domain. The NgCAM-NgCAM interaction could be established simultaneously with the axonin-1-NgCAM interaction. In contrast, the axonin-1-NgCAM interaction excluded axonin-1/axonin-1 binding. These results and the examination of the coclustering of axonin-1 and NgCAM at cell contacts, suggest that intercellular contact is mediated by a symmetric axonin-12/NgCAM2 tetramer, in which homophilic NgCAM binding across the extracellular space occurs simultaneously with a cis-heterophilic interaction of axonin-1 and NgCAM. The enhanced neurite fasciculation after overexpression of NgCAM by adenoviral vectors indicates that NgCAM is the limiting component for the formation of the axonin-12/NgCAM2 complexes and, thus, neurite fasciculation in DRG neurons.
authors.affiliation: Institute of Biochemistry, University of Zurich, CH-8057 Zurich, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Kunz
authors.forename: M
authors.initials: M
authors.lastname: Spirig
authors.forename: C
authors.initials: C
authors.lastname: Ginsburg
authors.forename: A
authors.initials: A
authors.lastname: Buchstaller
authors.forename: P
authors.initials: P
authors.lastname: Berger
authors.forename: R
authors.initials: R
authors.lastname: Lanz
authors.forename: C
authors.initials: C
authors.lastname: Rader
authors.forename: L
authors.initials: L
authors.lastname: Vogt
authors.forename: B
authors.initials: B
authors.lastname: Kunz
authors.forename: P
authors.initials: P
authors.lastname: Sonderegger
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D019062:Cell Adhesion Molecules, Neuron-Glia / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D002645:Chickens; D058969:Contactin 2; D005110:Extracellular Space / Q000502:physiology; D005727:Ganglia, Spinal / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D008958:Models, Molecular; D016296:Mutagenesis; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009924:Organ Culture Techniques; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D014162:Transfection
chemical_list: D019062:Cell Adhesion Molecules, Neuron-Glia; D015816:Cell Adhesion Molecules, Neuronal; C548675:Cntn2 protein, mouse; D058969:Contactin 2; D011994:Recombinant Proteins