Caveolae-dependent Endocytosis Is Required for Class A Macrophage Scavenger Receptor-mediated Apoptosis in Macrophages*
- Xu-Dong Zhu‡§,
- Yan Zhuang§,
- Jing-Jing Ben§,
- Ling-Ling Qian§,
- Han-Peng Huang§,
- Hui Bai§,
- Jia-Hao Sha‡,
- Zhi-Gang He¶ and
- Qi Chen‡§,1
- From the ‡Institute of Reproductive Medicine and
- §Atherosclerosis Research Center, Key Laboratory of Human Functional Genomics, Nanjing Medical University, Nanjing 210029, China and
- the ¶Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115
- 1 To whom correspondence should be addressed: Atherosclerosis Research Centre, Key Laboratory of Human Functional Genomics, Nanjing Medical University, Nanjing 210029, China. Tel.: 86-25-86862610; Fax: 86-25-86508960; E-mail: qichen{at}njmu.edu.cn.
Abstract
SR-A (class A macrophage 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.
Footnotes
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↵* This work was supported by National Natural Science Foundation of China Grants 30730044 and 81070120 and National Basic Research Program (973) Grant 2011CB503900 (to Q. C.) and National Natural Science Foundation of China Grant 81000118 (to J.-J. B.).
- Received May 18, 2010.
- Revision received September 9, 2010.
- © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
