Clathrin-dependent endocytosis is required for TrkB-dependent Akt-mediated neuronal protection and dendritic growth

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	Clathrin-dependent endocytosis is required for TrkB-dependent Akt-mediated neuronal protection and dendritic growth
	Xiong, Zhi-Qi
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2008
卷号	283 期号:19 页码:13280-13288
关键词	NEUROTROPHIC FACTOR SIGNALING PATHWAYS RECEPTOR INTERNALIZATION IN-VITRO SURVIVAL EXPRESSION KINASE CELLS BDNF NGF
ISSN号	0021-9258
通讯作者	Xiong, ZQ (reprint author), Chinese Acad Sci, Inst Neurosci, 320 Yueyang Rd, Shanghai 200031, Peoples R China,xiongzhiqi@ion.ac.cn
英文摘要	Endocytosis of Trk ((t) under bar ropomyosin-(r) under bar elated (k) under bar inase) receptors is critical for neurotrophin signal transduction and biological functions. However, the mechanism governing endocytosis of TrkB ((t) under bar ropomyosin-(r) under bar elated (k) under bar inase (B) under bar) and the specific contributions of TrkB endocytosis to downstream signaling are unknown. In this study, we report that blocking clathrin, dynamin, or AP2 in cultured neurons of the central nervous system inhibited brain-derived neurotrophic factor (BDNF)-induced activation of Akt but not ERK. Treating neurons with the clathrin inhibitor monodansylcadaverine or a peptide that blocks dynamin function specifically abrogated Akt pathway activation in response to BDNF but did not affect the response of other downstream effectors or the up-regulation of immediate early genes neuropeptide Y and activity-regulated cytoskeleton-associated protein. Similar effects were found in neurons expressing small interfering RNA to silence AP2 or a dominant negative form of dynamin that inhibits clathrin-mediated endocytosis. In PC12 cells, ERK but not Akt activation required TrkA endocytosis following stimulation with nerve growth factor, whereas the opposite was true when TrkA-expressing neurons were stimulated with nerve growth factor in the central nervous system. Thus, the specific effects of internalized Trk receptors probably depend on the presence of cell type-specific modulators of neurotrophin signaling and not on differences inherent to Trk receptors themselves. Endocytosis-dependent activation of Akt in neurons was found to be critical for BDNF-supported survival and dendrite outgrowth. Together, these results demonstrate the functional requirement of clathrin-and dynamin-dependent endocytosis in generating the full intracellular response of neurons to BDNF in the central nervous system.
学科主题	Biochemistry & Molecular Biology
收录类别	SCI
语种	英语
公开日期	2012-07-23
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1729]
专题	上海神经科学研究所_神经所(总) 上海神经科学研究所_疾病神经生物学研究组
推荐引用方式 GB/T 7714	Xiong, Zhi-Qi. Clathrin-dependent endocytosis is required for TrkB-dependent Akt-mediated neuronal protection and dendritic growth[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2008,283(19):13280-13288.
APA	Xiong, Zhi-Qi.(2008).Clathrin-dependent endocytosis is required for TrkB-dependent Akt-mediated neuronal protection and dendritic growth.JOURNAL OF BIOLOGICAL CHEMISTRY,283(19),13280-13288.
MLA	Xiong, Zhi-Qi."Clathrin-dependent endocytosis is required for TrkB-dependent Akt-mediated neuronal protection and dendritic growth".JOURNAL OF BIOLOGICAL CHEMISTRY 283.19(2008):13280-13288.