Cell‐cell adhesion by homophilic interaction of the neuronal recognition molecule axonin‐1

Abstract

The axonal surface glycoprotein axonin‐1, which occurs both as a glycosyl‐phosphatidylinositol‐anchored membrane‐bound form and a secreted form, promotes neurite outgrowth and is thought to be involved in axon‐guidance mechanisms in the developing nervous system. Recently, we have demonstrated that the neurite‐outgrowth‐promoting activity of axonin‐1, presented as substratum for cultured neurons, is mediated by a heterophilic interaction with the axonal glycoprotein neuronglia cell‐adhesion molecule (Ng‐CAM). Here we present evidence for homophilic (like‐like) binding among axonin‐1 molecules. Axonin‐1 was heterologously expressed in myeloma cells. Clonal cell lines, with exposed membrane‐bound axonin‐1 at their surface, formed large multicellular aggregates. Incubations of transfected and parental myeloma cells, under a series of different conditions, revealed homophilic axonin‐1/axonin‐1 interactions across the intermembrane space as the molecular mechanism promoting stable cell‐cell contacts. Using structural and functional characterisation, recombinant axonin‐1 was very similar to native axonin‐1, suggesting that homophilic axonin‐1 interactions are also established in neurons. The capability of axonin‐1 to interact with both Ng‐CAM and other axonin‐1 molecules might contribute to the formation of macromolecular networks at contact sites of growth cones and axons, comprising molecules of both membranes, and thus represent a mechanism for regulating neurite outgrowth and pathfinding. Copyright © 1993, Wiley Blackwell. All rights reserved