GP55 inhibits both cell adhesion and growth of neurons, but not non-neuronal cells via a G-protein-coupled receptor

There is compelling evidence for the role of inhibitory molecules in guiding neurons to their appropriate targets. Furthermore, continued expression of these molecules in the adult could explain why there is little regeneration of neurons in the central nervous system. We have previously identified a family of glycosyl phosphatidylinositol-linked glycoproteins (GP55) from adult chicken brain that has been shown to inhibit neurite outgrowth from dorsal root ganglion and forebrain neurons. GP55 consists of two or more glycoproteins and belongs to a subgroup of the Ig superfamily which contains OBCAM, LAMP, neurotrimin and CEPU-1. We now show that GP55 is anti-adhesive, blocking the adhesion of neurons to normally adhesive substrata in a concentration dependent manner. The anti-adhesive effect can be blocked using antiserum raised against GP55 and pertussis toxin (PTX) but not the beta oligomer alone. In contrast, the adhesion of fibroblasts and Schwann cells to the substrata is not affected by GP55. Indeed, non-neuronal cells spread and grow normally. These results would suggest that both the anti-adhesive effect and the inhibition of outgrowth by GP55 is specific to neurons and is mediated by a PTX sensitive, G-protein-coupled receptor.