Glycoprotein processing is required for completion but not initiation of oligodendroglial differentiation from its bipotential progenitor cell.
The role of N-linked glycoproteins in the development of oligodendroglia has been studied in a culture system that initially contains the progenitor cell for oligodendroglia and type 2 astrocytes. The progenitor cells, derived from mixed glial primary cultures of newborn rat cerebrum, were studied under culture conditions that we have shown previously to induce oligodendroglial differentiation. Castanospermine was used to inhibit processing of N-linked glycoproteins by its inhibitory action on glucosidase I, the enzyme responsible for the initial trimming of glucose residues from the glucosylated high mannose core oligosaccharide derived from the dolichol pathway. Exposure to castanospermine had no effect on the initial commitment of the progenitors to oligodendroglial differentiation, i.e. 95% of both control and castanospermine-treated cells became galactocerebroside (GC) positive. However, the developmental inductions of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) and glycerol-3-phosphate dehydrogenase (GPDH) and the elaboration of a network of fine interconnecting processes were prevented by the castanospermine exposure. No effect of castanospermine on cell number was observed. A major effect of the inhibitor on glycoprotein processing was manifested by an accumulation of high mannose glycoproteins, of abnormal oligosaccharide structure, compatible with the inhibition of glucosidase I.(ABSTRACT TRUNCATED AT 250 WORDS)
Ishii
S
S
Department of Neurology, Harvard Medical School, Boston, Mass.
Volpe
J J
JJ
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D001921:Brain / Q000166:cytology; D002240:Carbohydrate Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D004286:Dolichols / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D065089:Glycoside Hydrolase Inhibitors; D006031:Glycosylation; D007212:Indolizines / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects; D009844:Oligosaccharides / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology; D000520:alpha-Glucosidases / Q000378:metabolism; D054836:Indolizidines
D015415:Biomarkers; D004286:Dolichols; D006023:Glycoproteins; D065089:Glycoside Hydrolase Inhibitors; D007212:Indolizines; D009419:Nerve Tissue Proteins; D009844:Oligosaccharides; D000520:alpha-Glucosidases; C042059:glucosidase I; C037806:castanospermine; D054836:Indolizidines