title: Caveolae-dependent endocytosis is required for class A macrophage scavenger receptor-mediated apoptosis in macrophages.
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.
authors.affiliation: From the Institute of Reproductive Medicine and; Atherosclerosis Research Center, Key Laboratory of Human Functional Genomics, Nanjing Medical University, Nanjing 210029, China and.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Zhu
authors.affiliation: Atherosclerosis Research Center, Key Laboratory of Human Functional Genomics, Nanjing Medical University, Nanjing 210029, China and.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Atherosclerosis Research Center, Key Laboratory of Human Functional Genomics, Nanjing Medical University, Nanjing 210029, China and.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Ben
authors.affiliation: Atherosclerosis Research Center, Key Laboratory of Human Functional Genomics, Nanjing Medical University, Nanjing 210029, China and.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Qian
authors.affiliation: Atherosclerosis Research Center, Key Laboratory of Human Functional Genomics, Nanjing Medical University, Nanjing 210029, China and.
authors.forename: Han-Peng
authors.initials: HP
authors.lastname: Huang
authors.affiliation: Atherosclerosis Research Center, Key Laboratory of Human Functional Genomics, Nanjing Medical University, Nanjing 210029, China and.
authors.forename: Hui
authors.initials: H
authors.lastname: Bai
authors.affiliation: From the Institute of Reproductive Medicine and.
authors.forename: Jia-Hao
authors.initials: JH
authors.lastname: Sha
authors.affiliation: the Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: He
authors.affiliation: From the Institute of Reproductive Medicine and; Atherosclerosis Research Center, Key Laboratory of Human Functional Genomics, Nanjing Medical University, Nanjing 210029, China and. Electronic address: qichen@njmu.edu.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D021941:Caveolae / Q000378:metabolism*; D002460:Cell Line; D004705:Endocytosis / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D011134:Polysaccharides / Q000494:pharmacology; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000897:Anti-Ulcer Agents; D011134:Polysaccharides; D051117:Scavenger Receptors, Class A; C007789:fucoidan; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4