NEUROFASCIN INDUCES NEURITES BY HETEROPHILIC INTERACTIONS WITH AXONALNRCAM WHILE NRCAM REQUIRES F11 ON THE AXONAL SURFACE TO EXTEND NEURITES

Neurofascin and NrCAM are two axon-associated transmembrane glycoprote ins belonging to the L1 subgroup of the Ig superfamily. In this study, we have analyzed the interaction of both proteins using neurite outgr owth and binding assays. A neurofascin-Fc chimera was found to stimula te the outgrowth of tectal cells when immobilized on an inert surface but not as a soluble form using polylysine as substrate. Antibody bloc king experiments demonstrate that neurite extension on immobilized neu rofascin is mediated by NrCAM on the axonal surface. Under the reverse experimental conditions where NrCAM induces neurite extension, F11, a nd not neurofascin, serves as axonal receptor. Binding studies using t ransfected COS7 cells and immunoprecipitations reveal a direct interac tion between neurofascin and NrCAM. This binding activity was mapped t o the Ig domains within neurofascin. The neurofascin-NrCAM binding can be modulated by alternative splicing of specific stretches within neu rofascin. These studies indicate that heterophilic interactions betwee n Ig-like proteins implicated in axonal extension underlie a regulatio n by the neuron.