The myelin-associated glycoprotein (MAG) is a member of the immunoglobulin gene superfamily that is localized in the periaxonal interactions and may be involved in transmitting signals from axons to alternative splicing of its mRNA. The carbohydrate in MAG consists of a mixture of oligosaccharides, many of which are sialylated and sulfated and are currently being characterized. This year, we extended our previous studies on the abnormal expression of MAG isoforms and their glycosylation in dysmyelinating mice to trembler mutants that exhibit abnormalities of myelin restricted to the PNS. The relative expression of MAG isoforms was normal in the nerves of these mice, but PNS MAG contribute to the nerve pathology. In addition to our studies of MAG, a novel 80kDa glycoprotein in PNS and CNS myelin containing primarily The expression of MAG in cultured oligodendrocytes and Schwann cells continues to be studied to identify factors controlling its expression signaling. Recent experiments with immortalized Schwann cell lines indicate that expression of MAG and other myelin proteins are increased cell to cell contact. Although the control seems to be at the level of messenger RNAs, it is not associated with changes in cAMP levels, nor do nuclear runoff assays indicate it is at the transcriptional level. Experiments on the tyrosine phosphorylation of growth factor receptors in oligodendrocyte progenitors continued to determine whether the mechanism by which GM3 ganglioside enhances the expression of myelin components involves receptor modulation. Although these experiments have not so far uncovered a mechanism for the effect of GM3, they revealed a dramatic downstream effect of PDGF and FGF on the MAP kinase in these cells. Also our investigation of gangliosides in oligodendrocyte progenitors has shown that the A2B5 antibody, which is widely used to identify these cells, reacts most strongly with a novel ganglioside that is currently being characterized. Finally experiments to identify and characterize the putative MAG receptor in axonal surface expressing lines of oligodendrocytes and Schwann cells.
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