HAP1 is an in vivo UBE3A target that augments autophagy in a mouse model of Angelman syndrome

doi:10.1016/j.nbd.2019.104585

CORC > 成都生物研究所 > 中国科学院成都生物研究所 > 国家天然药物工程技术研究中心 > 天然产物研究

	HAP1 is an in vivo UBE3A target that augments autophagy in a mouse model of Angelman syndrome
	Wang, Tingting 5; Wang, Jingyu 5; Wang, Jie 3,4; Mao, Lin 5; Tang, Bin 5; Vanderklish, Peter W.2; Liao, Xun 1; Xiong, Zhi-Qi 3,4; Liao, Lujian 5
刊名	NEUROBIOLOGY OF DISEASE
	2019
卷号	132 页码:104585
关键词	UBE3A HAP1 Angelman syndrome autophagy SILAM Proteome
ISSN号	0969-9961
DOI	10.1016/j.nbd.2019.104585
产权排序	5
文献子类	Article
英文摘要	Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by maternal mutation and paternal imprinting of the gene encoding UBE3A, an E3 ubiquitin ligase. Although several potential target proteins of UBE3A have been reported, how these proteins regulate neuronal development remains unclear. We performed a large-scale quantitative proteomic analysis using stable-isotope labeling of amino acids in mammals (SILAM) in mice with maternal Ube3a mutation. We identified huntingtin (Htt)-associated protein (HAP1), a protein that is involved in Huntington's disease (HD), as a new target of UBE3A. We demonstrate that HAP1 regulates autophagy at the initiation stage by promoting PtdIns3K complex formation and enhancing its activity. HAP1 also co-localized with MAP1LC3 (LC3) and other proteins involved in autophagosome expansion. As a result, HAP1 increased autophagy flux. Strikingly, knocking down of HAP1 alleviated aberrant autophagy in primary neurons from AS mice. Concordantly, treatment of AS neurons with an autophagy inhibitor alleviated the reduction in density of dendritic spines. Furthermore, autophagy inhibition in AS mice partially alleviated a social interaction deficit as shown in open field test. Thus, our results identify HAP1 as an in vivo UBE3A target that contributes to deregulated autophagy and synaptic dysfunction in the central nervous system of AS mouse.
学科主题	Neurosciences & Behavior
URL标识	查看原文
WOS关键词	HUNTINGTIN-ASSOCIATED PROTEIN ; UBIQUITIN LIGASE ; MEDIATED DEGRADATION ; SYNAPSE ; PHOSPHORYLATION ; COMPLEX ; ATG14 ; LOCALIZES ; MUTATION ; RUBICON
WOS研究方向	Neurosciences & Neurology
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000497252500020
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/31066]
专题	国家天然药物工程技术研究中心_天然产物研究
通讯作者	Liao, Lujian
作者单位	1.Chinese Acad Sci, Chengdu Inst Biol, Chengdu 610041, Sichuan, Peoples R China 2.Scripps Res, Dept Mol Med, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA; 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Inst Neurosci,State Key Lab Neurosci, Shanghai 200031, Peoples R China; 5.East China Normal Univ, Sch Life Sci, Key Lab Brain Funct Genom, Shanghai Key Lab Regulatory Biol,Minist Educ, Shanghai 200241, Peoples R China;
推荐引用方式 GB/T 7714	Wang, Tingting,Wang, Jingyu,Wang, Jie,et al. HAP1 is an in vivo UBE3A target that augments autophagy in a mouse model of Angelman syndrome[J]. NEUROBIOLOGY OF DISEASE,2019,132:104585.
APA	Wang, Tingting.,Wang, Jingyu.,Wang, Jie.,Mao, Lin.,Tang, Bin.,...&Liao, Lujian.(2019).HAP1 is an in vivo UBE3A target that augments autophagy in a mouse model of Angelman syndrome.NEUROBIOLOGY OF DISEASE,132,104585.
MLA	Wang, Tingting,et al."HAP1 is an in vivo UBE3A target that augments autophagy in a mouse model of Angelman syndrome".NEUROBIOLOGY OF DISEASE 132(2019):104585.