Caveolae-dependent Endocytosis Is Required for Class A Macrophage Scavenger Receptor-mediated Apoptosis in Macrophages

被引:102
作者
Zhu, Xu-Dong [1 ,2 ]
Zhuang, Yan [1 ]
Ben, Jing-Jing [1 ]
Qian, Ling-Ling [1 ]
Huang, Han-Peng [1 ]
Bai, Hui [1 ]
Sha, Jia-Hao [2 ]
He, Zhi-Gang [3 ]
Chen, Qi [1 ,2 ]
机构
[1] Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China
[2] Nanjing Med Univ, Inst Reprod Med, Nanjing 210029, Peoples R China
[3] Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci, Boston, MA 02115 USA
基金
中国国家自然科学基金;
关键词
LOW-DENSITY-LIPOPROTEIN; FOAM CELL-FORMATION; CYTOPLASMIC DOMAIN; LIPID UPTAKE; PLASMA-MEMBRANE; CLATHRIN; ATHEROSCLEROSIS; INTERNALIZATION; BINDING; CHOLESTEROL;
D O I
10.1074/jbc.M110.145888
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
SR-A (classAmacrophage scavenger receptor) is a transmembrane receptor that can bind many different ligands, including modified lipoproteins that are relevant to the development of vascular diseases. However, the precise endocytic pathways of SR-A/mediated ligands internalization are not fully characterized. In this study, we show that the SR-A/ligand complex can be endocytosed by both clathrin-and caveolae-dependent pathways. Internalizations of SR-A-lipoprotein (such as acLDL) complexes primarily go through clathrin-dependent endocytosis. In contrast, macrophage apoptosis triggered by SR-A-fucoidan internalization requires caveolae-dependent endocytosis. The caveolae-dependent process activates p38 kinase and JNK signaling, whereas the clathrin-mediated endocytosis elicits ERK signaling. Our results suggest that different SR-A endocytic pathways have distinct functional consequences due to the activation of different signaling cascades in macrophages.
引用
收藏
页码:8231 / 8239
页数:9
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