Interaction between NG2 proteoglycan and PDGF alpha-receptor on O2A progenitor cells is required for optimal response to PDGF.

Previous studies on the NG2 chondroitin sulfate proteoglycan have shown that NG2 is expressed on A2B5-positive O2A progenitor cells, which are known to respond to platelet-derived growth factor (PDGF). In the accompanying paper (Nishiyama et al.; J Neurosci Res 43:299-314, 1996) we show that on O2A progenitors in the embryonic and newborn rat brain, NG2 and PDGF alpha-receptor display an extensive co-localization which becomes less pronounced as the brain matures past the first postnatal week. The present communication describes the relationship between NG2 and PDGF alpha-receptor in vitro. NG2 and PDGF alpha-receptor are highly co-localized on A2B5-positive O2A cells isolated from neonatal rat cerebrum. Mimicking the situation in vivo, the level of expression of the two molecules and the extent of co-localization decline as these cells differentiate into O4-positive pre-oligodendrocytes. However, maintenance of the cells in a progenitor state by treatment with bFGF results in increased levels of both NG2 and PDGF alpha-receptor on the cell surface, suggesting that expression of the two molecules may be coordinately regulated. Furthermore, NG2 can be co-immunoprecipitated from radiolabeled O2A extracts with a rabbit antibody to PDGF alpha-receptor, indicating the presence of a molecular complex that includes NG2 and the receptor. Finally, antibody-patching and subsequent down-regulation of NG2 results in reduced expression of PDGF alpha-receptor and diminishes the proliferative response of the cells to PDGF. These findings suggest that correct co-expression of the NG2 proteoglycan and PDGF alpha-receptor on the surface of O2A progenitor cells is important for the cells' ability to respond effectively to the mitogenic stimulus of PDGF.