LOX-1 scavenger receptor mediates calcium-dependent recognition of phosphatidylserine and apoptotic cells.
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.
Murphy
Jane E
JE
Endothelial Cell Biology Unit, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Tacon
Daryl
D
Tedbury
Philip R
PR
Hadden
Jonathan M
JM
Knowling
Stuart
S
Sawamura
Tatsuya
T
Peckham
Michelle
M
Phillips
Simon E V
SE
Walker
John H
JH
Ponnambalam
Sreenivasan
S
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*
C495137:OLR1 protein, human; D010718:Phosphatidylserines; D051127:Scavenger Receptors, Class E; D002118:Calcium