Lectin-glycan binding controls axon-myelin interactions

Axons are often ensheathed in myelin, a multi-layered membrane wrap. Myelin provides insulation with gaps where ion channels cluster, and is required for axon health and nerve conduction. Myelin-associated glycoprotein (MAG) on the inner myelin wrap binds to receptors on axons to support axon-myelin interactions. MAG is a lectin that binds to two sialoglycans on axons, gangliosides GD1a and GT1b. Studies of mice with altered ganglioside expression support the hypothesis that MAG-ganglioside binding is required for healthy axon-myelin interactions. Mag-null mice and mice lacking the MAG-binding glycan (B4galnt1-null mice) have the same axon-myelin phenotype: axon degeneration, altered axon structure, reduced conduction velocity, molecular abnormalities at nodes of Ranvier, hypersensitivity to axonal toxins, and motor behavioral deficits. We conclude that MAG-ganglioside binding is required for axon-myelin stability. MAG also inhibits axon outgrowth after traumatic injury. This negative effect of MAG is also due, in part, to sialoglycan binding. For some neurons in culture, axon outgrowth inhibition by MAG is reversed when gangliosides are modified or ganglioside expression is blocked. In spinal-injured rats, delivery of the ganglioside-modifying enzyme sialidase into the intrathecal space significantly improves motor recovery. These data support a role for MAG-ganglioside binding in axon-myelin stability and the control of axon outgrowth after injury.