Neurite fasciculation mediated by complexes of axonin-1 and Ng cell adhesion molecule

Neural cell adhesion molecules composed of immunoglobulin and fibronectin t ype III-like domains have been implicated in cell adhesion, neurite outgrow th, and fasciculation, Axonin-1 and Ng cell adhesion molecule (NgCAM), two molecules with predominantly axonal expression exhibit hemophilic interacti ons 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 hemophilic binding in the Ig domains 1-4 whereas he terophilic binding to axonin-1 was localized in the Ig domains 2-4 and the third FnIII domain. The NgCAM-NgCAM interaction could be established simult aneously with the axonin-1-NgCAM interaction. In contrast, the axonin-1-NgC AM interaction excluded axonin-1/axonin-1 binding. These results and the ex amination of the coclustering of axonin-1 and NgCAM at cell contacts, sugge st that intercellular contact is mediated by a symmetric axonin-1(2)/NgCAM( 2) tetramer, in which hemophilic NgCAM binding across the extracellular spa ce occurs simultaneously with a cis-heterophilic interaction of axonin-1 an d NgCAM. The enhanced neurite fasciculation after overexpression of NgCAM b y adenoviral vectors indicates that NgCAM is the limiting component for the formation of the axonin-1(2)/NgCAM(2) complexes and, thus, neurite fascicu lation in DRG neurons.