IDENTIFICATION OF MYELIN-ASSOCIATED GLYCOPROTEIN AS A MAJOR MYELIN-DERIVED INHIBITOR OF NEURITE GROWTH

Contact-dependent axon growth inhibitory activity is present in CNS my elin, but the inhibitory proteins have not been fully characterized. W e report here that at least two peaks of inhibitory activity can be se parated by fractionating solubilized CNS myelin proteins by DEAE chrom atography. A major peak of inhibitory activity corresponded to the elu tion profile of myelin-associated glycoprotein (MAC). Immunodepletion of MAG from these inhibitory fractions removed neurite growth inhibiti on, whereas recombinant MAC (ectodomain) was a potent inhibitor of neu rite outgrowth. Immunodepletion of MAG from total extracts of CNS myel in restored neurite growth up to 63% of control levels. These results establish that MAC is a significant, and possibly the major, inhibitor in CNS myelin; this has broad implications for axonal regeneration in the injured mammalian CNS.