Identification of podocalyxin-like protein as a high endothelial venule ligand for L-selectin: parallels to CD34.
The leukocyte adhesion molecule, L-selectin, mediates the recruitment of lymphocytes to secondary lymphoid organs via interactions with specific ligands presented on high endothelial venules (HEV). Although the HEV-derived ligands for L-selectin are still incompletely defined, they share a common sialomucin-like structure which is thought to present clustered oligosaccharides to the lectin domain of L-selectin. Podocalyxin-like protein (PCLP) is a transmembrane sialomucin that is similar in structure to the well-characterized L-selectin ligand CD34. PCLP has been shown previously to be expressed on the foot processes of podocytes in the kidney glomerulus as well as on vascular endothelium at some sites. We have determined that PCLP is present on HEV, where it binds to both recombinant L-selectin and the HEV-specific monoclonal antibody MECA-79. Furthermore, purified HEV-derived PCLP is able to support the tethering and rolling of lymphocytes under physiological flow conditions in vitro. These results suggest a novel function for PCLP as an adhesion molecule and allow the definition of conserved structural features in PCLP and CD34, which may be important for L-selectin ligand function.
Sassetti
C
C
Department of Anatomy, University of California, San Francisco, San Francisco, California 94143, USA.
Tangemann
K
K
Singer
M S
MS
Kershaw
D B
DB
Rosen
S D
SD
D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D001065:Appendix / Q000737:chemistry / Q000378:metabolism; D004729:Endothelium, Lymphatic / Q000737:chemistry / Q000378:metabolism*; D000939:Epitopes; D006801:Humans; D019169:Jurkat Cells; D019041:L-Selectin / Q000378:metabolism*; D008024:Ligands; D008208:Lymphatic System / Q000737:chemistry / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D014066:Palatine Tonsil / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012795:Sialoglycoproteins
D000954:Antigens, Surface; D000939:Epitopes; C069886:L-selectin counter-receptors; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D016201:Receptors, Lymphocyte Homing; D012795:Sialoglycoproteins; C001643:podocalyxin; D019041:L-Selectin