Molecular basis of interaction between NG2 proteoglycan and galectin-3.
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 alpha3beta1 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.
Wen
Yunfei
Y
Burnham Institute, Developmental Neurobiology Program, La Jolla, California 92037, USA. ywen@burnham.org
Makagiansar
Irwan T
IT
Fukushi
Jun-ichi
J
Liu
Fu-Tong
FT
Fukuda
Michiko N
MN
Stallcup
William B
WB
D000941:Antigens / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D037502:Galectin 3 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D005910:Glioma / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D037502:Galectin 3; D009844:Oligosaccharides; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4