Most of the current research on this project utilizes cultured Schwann cells or oligodendrocytes to investigate the expression and function of glycoproteins or glycolipids in their differentiation toward myelination. One aspect focuses on the myelin-associated glycoprotein (MAG) which is member of the IgG superfamily that is localized in periaxonal glial membranes of myelinated fibers and is thought to function in transmitting signals in both directions between axons and myelin-forming cells. Noteworthy advances in the past year include: 1) Demonstration that the phosphorylation of neurofilaments in dorsal root ganglion (DRG) neurons is greater when they are cocultured with MAG- expressing Schwann cells in comparison to MAG-negative Schwann cells. Thus, this culture system provides a good in vitro model to investigate the signaling mechanisms mediating the alterations of neurofilament phosphorylation observed in vivo in MAG knockout mice. 2) Identification and characterization of a 250 kD glycoprotein that binds MAG and appears to a good candidate to be one of its neuronal ligands. Another aspect of our research in the past year concerned the expression and function of gangliosides in differentiating oligodendrocytes. Our previous research had shown that increased expression of GM3 ganglioside enhanced differentiation toward myelination, possibly by modulating the activity of growth factor receptors. This led to an investigation of the action of growth factors on oligodendrocyte progenitators, especially a comparison of the effects of platelet derived growth factor (PDGF) and fibroblast growth factor (FGF), both of which activate MAP kinase in the cells. Despite their similar effects on MAP kinase, there are a number of differences in their mode of action such as the kinetics of MAP kinase activation, extent of receptor tyrosine phosphorylation, and modulation of their effects by protein kinase C. Also we made some notable observations with regard to quantitatively minor gangliosides expressed by oligodendrocyte progenitors. First, these cells express several sulfated gangliosides, and this novel class of glycolipids had not previously been described in neural tissue. Second, we have shown that oligodendrocyte progenitors express O-acetylated gangliosides, and O-acetyl-GT3 is the principal glycolipid antigen reacting wit the A2B5 antibody that is widely used to identify these cells.
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