LOX-1 scavenger receptor mediates calcium-dependent recognition of phosphatidylserine and apoptotic cells

• Published in: Biochemical journal Vol. 393; no. Pt 1; pp. 107 - 115
• Main Authors: Murphy, Jane E, Tacon, Daryl, Tedbury, Philip R, Hadden, Jonathan M, Knowling, Stuart, Sawamura, Tatsuya, Peckham, Michelle, Phillips, Simon E V, Walker, John H, Ponnambalam, Sreenivasan
• Format: Journal Article
• Language: English
• Published: England Portland Press Ltd 01.01.2006
• Subjects: Animals; Apoptosis; Calcium - metabolism; Calcium - pharmacology; Cell Line; Gene Expression Regulation; Humans; Phosphatidylserines - metabolism; Protein Binding; Scavenger Receptors, Class E - metabolism
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj20051166

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.