Molecular basis of interaction between NG2 proteoglycan and galectin-3

✍ Scribed by Yunfei Wen; Irwan T. Makagiansar; Jun-ichi Fukushi; Fu-Tong Liu; Michiko N. Fukuda; William B. Stallcup

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 370 KB
• Volume: 98
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20768

✦ Synopsis

Previous work has demonstrated the ability of the NG2 proteoglycan, a component of microvascular pericytes, to stimulate endothelial cell motility and morphogenesis. This function of NG2 depends on formation of a complex with galectin-3 and a3b1 integrin to stimulate integrin-mediated transmembrane signaling. In addition, the co-expression of galectin-3 and NG2 in A375 melanoma cells suggests that the malignant properties of these cells may be affected by interaction between the two molecules. Here, we extend the theme of co-expression and interaction of NG2 and galectin-3 to human glioma cells. We also establish a molecular basis for the NG2/galectin-3 interaction. The C-terminal carbohydrate recognition domain of galectin-3 is responsible for binding to the NG2 core protein. Within the NG2 extracellular domain, the membrane-proximal D3 segment of the proteoglycan contains the primary binding site for interaction with galectin-3. The interaction between galectin-3 and NG2 is a carbohydrate-dependent one mediated by N-linked rather than O-linked oligosaccharides within the D3 domain of the NG2 core protein. These studies establish a foundation for attempts to reduce the aggressive properties of tumor cells by disrupting the NG2/galectin-3 interaction.