Endoglycan, a member of the CD34 family, functions as an L-selectin ligand through modification with tyrosine sulfation and sialyl Lewis x.
During lymphocyte homing to secondary lymphoid organs and instances of inflammatory trafficking, the rolling of leukocytes on vascular endothelium is mediated by transient interactions between L-selectin on leukocytes and several carbohydrate-modified ligands on the endothelium. Most L-selectin ligands such as CD34 and podocalyxin present sulfated carbohydrate structures (6-sulfated sialyl Lewis x or 6-sulfo-sLex) as a recognition determinant within their heavily glycosylated mucin domains. We recently identified endoglycan as a new member of the CD34 family. We report here that endoglycan, like the two other members of this family (CD34 and podocalyxin) can function as a L-selectin ligand. However, endoglycan employs a different binding mechanism, interacting with L-selectin through sulfation on two tyrosine residues and O-linked sLex structures that are presented within its highly acidic amino-terminal region. Our analysis establishes striking parallels with PSGL-1, a leukocyte ligand that interacts with all three selectins, mediating leukocyte-endothelial, leukocyte-leukocyte, and platelet-leukocyte interactions. Since the distribution of endoglycan includes hematopoietic precursors and leukocyte subpopulations, in addition to endothelial cells, our findings suggest several potential settings for endoglycan-mediated adhesion events.
Fieger
Claudia B
CB
Department of Anatomy, Program in Immunology, University of California, San Francisco, California 94143-0452, USA.
Sassetti
Christopher M
CM
Rosen
Steven D
SD
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D050260:Carbohydrate Metabolism; D002448:Cell Adhesion; D006224:Cricetinae; D018076:DNA, Complementary / Q000378:metabolism; D019281:Dimerization; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D019041:L-Selectin / Q000378:metabolism*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009077:Mucins / Q000378:metabolism / Q000502:physiology*; D009844:Oligosaccharides / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D000080506:Sialyl Lewis X Antigen; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism*
D018076:DNA, Complementary; D008024:Ligands; D008562:Membrane Glycoproteins; D009077:Mucins; D009844:Oligosaccharides; C084882:P-selectin ligand protein; D011993:Recombinant Fusion Proteins; D000080506:Sialyl Lewis X Antigen; C406902:endoglycan; D019041:L-Selectin; D014443:Tyrosine