title: LOX-1 scavenger receptor mediates calcium-dependent recognition of phosphatidylserine and apoptotic cells.
abstract: The LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1) scavenger receptor regulates vascular responses to oxidized-low-density-lipoprotein particles implicated in atherosclerotic plaque formation. LOX-1 is closely related to C-type lectins, but the mechanism of ligand recognition is not known. Here we show that human LOX-1 recognizes a key cellular phospholipid, PS (phosphatidylserine), in a Ca2+-dependent manner, both in vitro and in cultured cells. A recombinant, folded and glycosylated LOX-1 molecule binds PS, but not other phospholipids. LOX-1 recognition of PS was maximal in the presence of millimolar Ca2+ levels. Mg2+ was unable to substitute for Ca2+ in LOX-1 binding to PS, indicating a Ca2+-specific requirement for bivalent cations. LOX-1-mediated recognition of PS-containing apoptotic bodies was dependent on Ca2+ and was decreased to background levels by bivalent-cation chelation, LOX-1-blocking antibodies or PS-containing liposomes. The LOX-1 membrane protein is thus a Ca2+-dependent phospholipid receptor, revealing novel recognition of phospholipids by mammalian lectins.
authors.affiliation: Endothelial Cell Biology Unit, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Murphy
authors.forename: Daryl
authors.initials: D
authors.lastname: Tacon
authors.forename: Philip R
authors.initials: PR
authors.lastname: Tedbury
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Hadden
authors.forename: Stuart
authors.initials: S
authors.lastname: Knowling
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawamura
authors.forename: Michelle
authors.initials: M
authors.lastname: Peckham
authors.forename: Simon E V
authors.initials: SE
authors.lastname: Phillips
authors.forename: John H
authors.initials: JH
authors.lastname: Walker
authors.forename: Sreenivasan
authors.initials: S
authors.lastname: Ponnambalam
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D010718:Phosphatidylserines / Q000378:metabolism*; D011485:Protein Binding; D051127:Scavenger Receptors, Class E / Q000378:metabolism*
chemical_list: C495137:OLR1 protein, human; D010718:Phosphatidylserines; D051127:Scavenger Receptors, Class E; D002118:Calcium