SOLUBLE MYELIN-ASSOCIATED GLYCOPROTEIN (MAG) FOUND IN-VIVO INHIBITS AXONAL REGENERATION

Myelin-associated glycoprotein (MAG) is a potent inhibitor of axonal r egeneration when used as a substrate for growth. However, to be charac terized definitively as inhibitory rather than nonpermissive, MAG must also inhibit axonal regeneration when presented in solution. Here, we show that soluble dMAG (extracellular domain only), released in abund ance from myelin and found in vivo and chimeric MAG-Fc, can potently i nhibit axonal regeneration. For both dMAG and MAG-Fc, inhibition is do se-dependent. If myelin-conditioned medium is immunodepleted of dMAG, or if a MAG antibody is included with MAG-Fc, inhibition is completely neutralized. Together with MAG's ability to induce growth cone collap se, these results demonstrate that MAG is an inhibitory molecule and n ot merely nonpermissive. The results also suggest that MAG binds to a specific receptor and initiates a signal transduction cascade to effec t inhibition. Importantly, these results indicate that soluble dMAG de tected in vivo could contribute to the lack of regeneration in the mam malian CNS after injury.