Molecular cloning of a dendritic cell-associated transmembrane protein, DC-HIL, that promotes RGD-dependent adhesion of endothelial cells through recognition of heparan sulfate proteoglycans.
We isolated a novel molecule (DC-HIL) expressed abundantly by the XS52 dendritic cell (DC) line and epidermal Langerhans cells, but minimally by other cell lines. DC-HIL is a type I transmembrane protein that contains a heparin-binding motif and an integrin-recognition motif, RGD, in its extracellular domain (ECD). A soluble fusion protein (DC-HIL-Fc) of the ECD and an immunoglobulin Fc bound to the surface of an endothelial cell line (SVEC). This binding induced adhesion of SVEC to its immobilized form. Sulfated polysaccharides (e.g. heparin and fucoidan) inhibited binding of soluble DC-HIL-Fc and adhesion of SVEC. By contrast, an integrin inhibitor (RGDS tetramer) had no effect on binding to SVEC, but prevented adhesion of SVEC. This differential RGD requirement was confirmed by the finding that DC-HIL-Fc mutant lacking the RGD motif can bind to SVEC but is unable to induce adhesion of SVEC. Furthermore, DC-HIL appears to recognize directly these sulfated polysaccharides. These results suggest that DC-HIL binds to SVEC by recognizing heparan sulfate proteoglycans on endothelial cells, thereby inducing adhesion of SVEC in an RGD-dependent manner. We propose that DC-HIL serves as a DC-associated, heparan sulfate proteoglycan-dependent integrin ligand, which may be involved in transendothelial migration of DC.
Shikano
S
S
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9069, USA.
Bonkobara
M
M
Zukas
P K
PK
Ariizumi
K
K
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D003001:Cloning, Molecular; D003713:Dendritic Cells / Q000737:chemistry* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D005136:Eye Proteins; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
D005136:Eye Proteins; C445671:Gpnmb protein, mouse; D019812:Heparan Sulfate Proteoglycans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009842:Oligopeptides; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C047981:arginyl-glycyl-aspartic acid