Biosynthesis and post-translational processing of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) -: N-linked glycosylation affects cell-surface expression and ligand binding

被引:63
作者
Kataoka, H
Kume, N
Miyamoto, S
Minami, M
Murase, T
Sawamura, T
Masaki, T
Hashimoto, N
Kita, T
机构
[1] Kyoto Univ, Grad Sch Med, Dept Geriatr Med, Sakyo Ku, Kyoto 6068507, Japan
[2] Kyoto Univ, Grad Sch Med, Dept Neurosurg, Sakyo Ku, Kyoto 6068507, Japan
[3] Natl Cardiovasc Ctr, Res Inst, Dept Biosci, Osaka 5658565, Japan
关键词
D O I
10.1074/jbc.275.9.6573
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
LOX-1 (lectin-like oxidized low density lipoprotein receptor-1) is a type II membrane protein belonging to the C-type lectin family that can act as a cell-surface receptor for atherogenic oxidized low density lipoprotein (Ox-LDL) and may play crucial roles in atherogenesis. In this study, we show, by pulse-chase labeling and glycosidase digestion, that LOX-1 is synthesized as a 40-kDa precursor protein with N-linked high mannose carbohydrate chains (pre-LOX-1), which is subsequently further glycosylated and processed into the 48-kDa mature form within 40 min, Furthermore, when treated with an N-glycosylation inhibitor, tunicamycin, both tumor necrosis factor-alpha-activated bovine aortic endothelial cells and CHO-K1 cells stably expressing bovine LOX-1 (BLOX-1-CHO) exclusively produced a 32-kDa deglycosylated form of LOX-1, Cell enzyme-linked immunosorbent assay, flow cytometry, and immunofluorescence confocal microscopy demonstrated that the deglycosylated form of LOX-1 is not efficiently transported to the cell surface, but is retained in the endoplasmic reticulum or Golgi apparatus in tumor necrosis factor-alpha-activated bovine aortic endothelial cells, but not in BLOX-1-CHO cells. Radiolabeled Ox-LDL binding studies revealed that the deglycosylated form of LOX-1 expressed on the cell surface of BLOX-1-CHO cells has a reduced affinity for Ox-LDL binding, Taken together, N-linked glycosylation appears to play key roles in the cell-surface expression and ligand binding of LOX-1.
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页码:6573 / 6579
页数:7
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