Myelin-associated glycoprotein inhibits axonal regeneration from a variety of neurons via interaction with a sialoglycoprotein

Abstract

Myelin-associated glycoprotein (MAG) is a potent inhibitor of axonal regeneration from both cerebellar neurons and adult dorsal root ganglion (DRG) neurons. In contrast, MAG promotes axonal growth from newborn DRG neurons. Here, we show that the switch in response to MAG from promotion to inhibition of neurite outgrowth by DRg neurons occurs sharply at Postnatal Day 3. To date, of all the neurons tested a postnatal switch in response is only observed for DRG neurons; MAG inhibits axonal growth from retinal, superior cervical ganglion, spinal, and hippocampal neurons of all postnatal ages. Furthermore, MAG binds to neurons from which it promotes and from which it inhibits outgrowth, in a sialic-acid-dependent manner. Now we show this binding is also trypsin-sensitive. Hence, the interaction is via a sialoglycoprotein. Binding of MAG to all the neurons tested here was also sialic-acid-dependent. Importantly, both inhibition and promotion of neurite outgrowth by MAG are reduced, or abolished completely, either by desialyation of the neurons prior to the outgrowth assay or by including small sialic-acid-bearing sugars in the cultures. These results suggest that MAG is likely to contribute to the lack of regeneration observed throughout the nervous system. Also, it is likely that MAG is exerting its effect, either directly or indirectly, on both promotion and inhibition of neurite outgrowth via a neuronal sialoglycoprotein.