CELL-CELL ADHESION BY HOMOPHILIC INTERACTION OF THE NEURONAL RECOGNITION MOLECULE AXONIN-1

The axonal surface glycoprotein axonin-1, which occurs both as a glyco syl-phosphatidylinositol-anchored membrane-bound form and a secreted f orm, promotes neurite outgrowth and is thought to be involved in axon- guidance mechanisms in the developing nervous system. Recently, we hav e demonstrated that the neurite-outgrowth-promoting activity of axonin -1, presented as a substratum for cultured neurons, is mediated by a h eterophilic interaction with the axonal glycoprotein neuron-glia cell- adhesion molecule (Ng-CAM). Here we present evidence for homophilic (l ike-like) binding among axonin-1 molecules. Axonin-1 was heterologousl y expressed in myeloma cells. Clonal cell lines, with exposed membrane -bound axonin-1 at their surface, formed large multicellular aggregate s. Incubations of transfected and parental myeloma cells, under a seri es of different conditions, revealed homophilic axonin-1/axonin-I inte ractions across the intermembrane space as the molecular mechanism pro moting stable cell-cell contacts. Using structural and functional char acterisation, recombinant axonin-I was very similar to native axonin-1 , suggesting that homophilic axonin-1 interactions are also establishe d in neurons. The capability of axonin-1 to interact with both Ng-CAM and other axonin-I molecules might contribute to the formation of macr omolecular networks at contact sites of growth cones and axons, compri sing molecules of both membranes, and thus represent a mechanism for r egulating neurite outgrowth and pathfinding.