Myelin-associated glycoprotein interacts with ganglioside GT1b - A mechanism for neurite outgrowth inhibition

Myelin-associated glycoprotein (MAG) is expressed on myelinating glia and i nhibits neurite outgrowth from post-natal neurons. MAG has a sialic acid bi nding site in its N-terminal domain and binds to specific sialylated glycan s and gangliosides present on the surface of neurons, but the significance of these interactions in the effect of MAG on neurite outgrowth is unclear. Here we present evidence to suggest that recognition of sialylated glycans is essential for inhibition of neurite outgrowth by MAG. Arginine 118 on M AG is known to make a key contact with sialic acid. me show that mutation o f this residue reduces the potency of MAG inhibitory activity hut that resi dual activity is also a result of carbohydrate recognition. me then go on t o investigate gangliosides GT1b and GD1a as candidate MAG receptors. me sho w that MAG specifically binds both gangliosides and that both are expressed on the surface of MAG-responsive neurons. Furthermore, antibody cross-link ing of cell surface GT1b, but not GD1a, mimics the effect of MAG, in that n eurite outgrowth is inhibited through activation of Rho kinase, These data strongly suggest that interaction with GT1b on the neuronal cell surface is a potential mechanism for inhibition of neurite outgrowth by MAG.