RAPID CONVERSION OF MYELIN-ASSOCIATED GLYCOPROTEIN TO A SOLUBLE DERIVATIVE IN PRIMATES

Myelin-associated glycoprotein (MAG) is susceptible to proteolysis by a calcium-activated neutral protease which is located in myelin. The c onversion of MAG (M(r) 100,000) to its soluble derivative dMAG (M(r) 9 0,000) occurs much more rapidly in myelin from human white matter than in myelin from rat brain, and the rate of formation of dMAG is increa sed even more in myelin from white matter of patients with multiple sc lerosis (MS). The MAG to dMAG conversion was studied in several specie s, ranging from mice to non-human primates and humans to determine wha t animal model would be the most appropriate for investigating the MAG to dMAG reaction in demyelinating disorders. Myelin fractions from br ains of these species were prepared and incubated at 37 degrees C in 0 .2 M NH4HCO3, pH 7.4 for time periods ranging from 5 min to 24 h. West ern blot analysis of the samples, taken at the end points of the diffe rent incubation periods, showed that the time required for a 50% conve rsion of MAG to dMAG was 18-24 h in myelin from rodents to bovine. The non-human primate studies revealed a 50% conversion at 2 h for marmos et samples and rhesus monkey samples, 20 min for gorilla samples and 1 0 min for chimpanzee samples. Human myelin samples needed only 5 min f or a 50% conversion of MAG to dMAG. The reason for the significantly f aster formation of dMAC in primate myelin is unknown and currently is being investigated.