Specific N-Linked Oligosaccharides Are Required for Oligodendroglial Differentiation but Probably Not for Astrocytic Differentiation

Abstract

Primary cultures of cerebral glia derived from neonatal rat brain were utilized to determine whether specific glycoproteins are involved in oligodendroglial and astrocytic differentiation. Specific emphasis was placed on the oligosaccharide portion of glycoproteins, and inhibitors of glycoprotein processing were studied. Castanospermine, an inhibitor of glucosidase I, and thereby formation of both complex glycoproteins and high mannose glycoproteins, and deoxymannojirimycin (DMM), an inhibitor of mannosidase I and thereby formation of complex glycoproteins, were utilized. Castanospermine exposure prevented the developmental inductions of the two oligodendroglial markers, 2',3'-cyclic nucleotide 3'-phosphohydrolase and glycerol-3-phosphate dehydrogenase. The effect of castanospermine on oligodendroglial differentiation was reversible. In contrast, castanospermine had no effect on the developmental inductions of the two astrocytic markers, glutamine synthetase and lactate dehydrogenase. DMM exposure had no effect on either oligodendroglial or astrocytic differentiation. Although both inhibitors caused a marked decrease in the formation of complex glycoproteins and an increase in high mannose structures, the oligosaccharide composition of these high mannose structures differed markedly. Castanospermine caused an increase in 'abnormal', apparently glucosylated high mannose structures and a decrease in all other 'normal' high mannose oligosaccharides, whereas DMM caused an increase in most high mannose structures, especially those migrating in the region of the Man7GlcNAc standard. The data indicate that oligodendroglial differentiation requires specific N-linked oligosaccharides, probably principally of the high mannose type, and that astrocytic differentiation can proceed normally despite marked alterations in both complex and high mannose glycoproteins.