Neurite fasciculation mediated by complexes of axonin-1 and Ng cell adhesion molecule.
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.
Kunz
S
S
Institute of Biochemistry, University of Zurich, CH-8057 Zurich, Switzerland.
Spirig
M
M
Ginsburg
C
C
Buchstaller
A
A
Berger
P
P
Lanz
R
R
Rader
C
C
Vogt
L
L
Kunz
B
B
Sonderegger
P
P
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
D019062:Cell Adhesion Molecules, Neuron-Glia; D015816:Cell Adhesion Molecules, Neuronal; C548675:Cntn2 protein, mouse; D058969:Contactin 2; D011994:Recombinant Proteins