title: Endoglycan, a member of the CD34 family, functions as an L-selectin ligand through modification with tyrosine sulfation and sialyl Lewis x.
abstract: 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.
authors.affiliation: Department of Anatomy, Program in Immunology, University of California, San Francisco, California 94143-0452, USA.
authors.forename: Claudia B
authors.initials: CB
authors.lastname: Fieger
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Sassetti
authors.forename: Steven D
authors.initials: SD
authors.lastname: Rosen
mesh_terms: 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*
chemical_list: 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