Interaction between NG2 proteoglycan and PDGF α‐receptor on O2A progenitor cells is required for optimal response to PDGF

Abstract

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 α-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 α-receptor in vitro. NG2 and PDGF α-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 α-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 α-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 α-receptor and diminishes the proliferative response of the cells to PDGF. These findings suggest that correct co-expression of the NG2 proteoglycan and PDGF α-receptor on the surface of O2A progenitor cells is important for the cells' ability to respond effectively to the mitogenic stimulus of PDGF. © 1996 Wiley-Liss, Inc.