PG-M/versican binds to P-selectin glycoprotein ligand-1 and mediates leukocyte aggregation

• Published in: Journal of cell science Vol. 117; no. Pt 24; pp. 5887 - 5895
• Main Authors: Zheng, Peng-Sheng, Vais, Dana, Lapierre, David, Liang, Yao-Yun, Lee, Vivian, Yang, Bing L, Yang, Burton B
• Format: Journal Article
• Language: English
• Published: England 15.11.2004
• Subjects: Amino Acid Motifs; Binding Sites; Cell Adhesion; Cell Line, Tumor; Cell Membrane - metabolism; Chondroitin Sulfate Proteoglycans - metabolism; Chondroitin Sulfate Proteoglycans - physiology; Disulfides - chemistry; Dithiothreitol - pharmacology; DNA Primers - chemistry; DNA, Complementary - metabolism; Gene Library; Glutathione Transferase - metabolism; Glycoproteins - chemistry; Humans; Leukocytes - cytology; Leukocytes - metabolism; Matrix Metalloproteinases - chemistry; Membrane Glycoproteins - metabolism; Models, Biological; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - physiology; Protein Binding; Protein Structure, Tertiary; Recombinant Fusion Proteins - chemistry; Recombinant Proteins - chemistry; Signal Transduction; Transfection; Two-Hybrid System Techniques; Versicans
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.01516

P-selectin glycoprotein ligand-1 (PSGL-1), a glycoprotein expressed on the cell surface of leukocytes, binds to selectins and mediates leukocyte rolling on the vascular endothelium. Here we report that PSGL-1 binds to the C-terminal (G3 domain) of the extracellular proteoglycan PG-M/versican. Cells transfected with PSGL-1 or a shorter form containing the binding site, or cells expressing endogenous PSGL-1 aggregate in the presence of versican or G3 product. The aggregation appears to be induced by G3 multimers that bind to PSGL-1 and form a network. Endogenous versican and/or G3-containing fragments also bind to PSGL-1 in human plasma. Removal of the endogenous G3-containing fragments reduces the effect of plasma on leukocyte aggregation. Finally, the roles of G3-containing fragments in leukocyte aggregation were confirmed in a mouse model. Taken together, our results strongly support a physiologically relevant role for PSGL-1/versican binding and may have implications in the immunoresponse.