Glycoprotein Processing Is Required for Completion But Not Initiation of Oligodendroglial Differentiation from Its Bipotential Progenitor Cell (original) (raw)
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Research Articles| December 23 1992
Department of Neurology, Harvard Medical School and Children's Hospital, Boston, Mass., USA
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Department of Neurology, Harvard Medical School and Children's Hospital, Boston, Mass., USA
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Dev Neurosci (1992) 14 (3): 221–229.
Abstract
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. The data led to the following conclusions: (1) N-linked glycoprotein processing is not required for the initial expression of oligodendroglial differentiation; (2) such processing is required for later phases of oligodendroglial differentiation, i.e. full induction of CNP and GPDH and elaboration of fine, interconnecting processes, and (3) N-linked glycoproteins, particularly high mannose glycoproteins of normal structure, are critical for the progression of oligodendroglial differentiation.
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© 1992 S. Karger AG, Basel
1992
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