Molecular biology of ryudocan, an endothelial heparan sulfate proteoglycan.
Ryudocan is a type I integral membrane heparan sulfate proteoglycan, which was originally cloned from rat microvascular endothelial cells. We have cloned the cDNA of rat ryudocan. The deduced amino acids of ryudocan has homologous transmembrane and intracellular domains with syndecan but very distinct extracellular regions. We also cloned the human ryudocan cDNA, of which the gene localizes on the chromosome 20q12. To better understand the regulation of ryudocan expression, we have determined the structural organization of the human ryudocan gene. The human ryudocan gene extends approximately 24 kb and is divided into five exons that appear conserved in syndecan family members. The 5'-flanking sequences of the human ryudocan gene contain a variety of potential binding sites for transcription factors and are capable of functioning as a promoter. We purified human ryudocan and evaluated its interactions with several extracellular ligands. It was found that basic fibroblast growth factor (bFGF), midkine, and tissue factor pathway inhibitor exhibited significant ryudocan bindings. Heparitinase, but not chondroitin ABC lyase treatment, destroyed those ryudocan bindings; thus, the heparan sulfate chains of ryudocan appear to be responsible for those bindings. Immunohistochemical analysis revealed that ryudocan is expressed in peripheral nerve tissues, fibrous connective tissues, and placental trophoblasts. These findings suggest that ryudocan may possess multiple biologic functions, such as bFGF modulation, neurite growth promotion, and anticoagulation, via heparan sulfate-binding effectors in the cellular microenvironment.
Kojima
T
T
Department of Medical Technology, Nagoya University School of Health Sciences, Japan.
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D003001:Cloning, Molecular; D016207:Cytokines; D018076:DNA, Complementary / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005796:Genes; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins; D000078792:Midkine; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D009928:Organ Specificity; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011509:Proteoglycans / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D053671:Syndecan-4; D013925:Thromboplastin / Q000378:metabolism
D002352:Carrier Proteins; D016207:Cytokines; D018076:DNA, Complementary; D019812:Heparan Sulfate Proteoglycans; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; C508304:SDC4 protein, human; C508307:Sdc4 protein, rat; D053671:Syndecan-4; D016222:Fibroblast Growth Factor 2; D000078792:Midkine; D013925:Thromboplastin; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase