PG-M/versican binds to P-selectin glycoprotein ligand-1 and mediates leukocyte aggregation.
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.
Zheng
Peng-Sheng
PS
Sunnybrook and Women's College Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
Vais
Dana
D
Lapierre
David
D
Liang
Yao-Yun
YY
Lee
Vivian
V
Yang
Bing L
BL
Yang
Burton B
BB
D020816:Amino Acid Motifs; D001665:Binding Sites; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism / Q000502:physiology*; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry; D004229:Dithiothreitol / Q000494:pharmacology; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction; D014162:Transfection; D020798:Two-Hybrid System Techniques; D053675:Versicans
D011508:Chondroitin Sulfate Proteoglycans; D017931:DNA Primers; D018076:DNA, Complementary; D004220:Disulfides; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C084882:P-selectin ligand protein; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C508322:VCAN protein, human; C508323:Vcan protein, mouse; D053675:Versicans; D005982:Glutathione Transferase; D020782:Matrix Metalloproteinases; D004229:Dithiothreitol