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.
Nishiyama
A
A
La Jolla Cancer Research Foundation, California, USA.
Lin
X H
XH
Giese
N
N
Heldin
C H
CH
Stallcup
W B
WB
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D000941:Antigens / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007700:Kinetics; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology*; D012516:Osteosarcoma; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011509:Proteoglycans / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000099216:Chondroitin Sulfate Proteoglycan 4
D000906:Antibodies; D000941:Antigens; D016222:Fibroblast Growth Factor 2; D010982:Platelet-Derived Growth Factor; D011509:Proteoglycans; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor; D000099216:Chondroitin Sulfate Proteoglycan 4