title: Truncation of the N-terminal ectodomain has implications in the N-glycosylation and transport to the cell surface of Edg-1/S1P1 receptor.
abstract: The endothelial cell-expressed sphingosine 1-phosphate receptors Edg-1/S1P1 and Edg-3/S1P3 have been implicated in various physiological events such as the regulation of angiogenesis. Since there is an excess of a ligand constitutively in blood, these receptors may have some mechanism(s) avoiding overstimulation. In this study, we found that the N-terminal ectodomains of Edg-1/S1P1 and Edg-3/S1P3 were truncated in overexpressing cells. The truncated form of Edg-1/S1P1 expressed on the cell surface had undergone complex-type oligosaccharide modification at the Golgi. A deletion mutant lacking the N-terminal processing domain of Edg-1/S1P1 accumulated in the endoplasmic reticulum, and was not expressed on the cell surface. When a basic amino acid residue was introduced at the cleavage site of Edg-1/S1P1, the molecular weight of the glycosylated protein was greater in the mutant compared to the wild type, due to the bound oligosaccharide. These results demonstrated that the structure of the N-terminal ectodomain of Edg-1/S1P1 affects both its transport to the cell surface and the N-glycosylation process. Ectodomain shedding of many membrane proteins has been implicated in various diseases. Therefore, N-terminal processing of Edg-1/S1P1 and Edg-3/S1P3 might play roles in endothelial cell functions.
authors.affiliation: Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Nishi 6, Kita 12, Kita-ku, Sapporo 060-0812.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kohno
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Igarashi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006031:Glycosylation; D008246:Lysophospholipids / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D049312:Receptors, Lysophospholipid; D049349:Receptors, Lysosphingolipid; D017384:Sequence Deletion / Q000235:genetics*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D000081025:Sphingosine-1-Phosphate Receptors; D055672:Static Electricity
chemical_list: D008246:Lysophospholipids; D009844:Oligosaccharides; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; C060506:sphingosine 1-phosphate; D013110:Sphingosine