Excessive UBE3A dosage impairs retinoic acid signaling and synaptic plasticity in autism spectrum disorders

查看全文 作　　者：Xingxing [1]Xu;Chuanyin [1,2]Li;Xiaobo [1,2]Gao;Kun [3]Xia;Hui [3]Guo;Yali [1]Li;[1,2]ZijianHao;Lei [1]Zhang;Daming [1]Gao;Chenfan [1]Xu;Huatai [4]Xu;Zhi-Qi [4]Xiong;Zilong [4]Qiu;Ling [5]Mei;Xiaoduo [1]Xie;Kangcheng [1]Ruan;Ronggui [1]Hu

机构地区：[1]Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China;[2]University of Chinese Academy of Sciences, Shanghai 200031, China;[3]The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, China;[4]Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and lntelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China;[5]Department of Medicine, Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA

出　　处：《Cell Research》索引2018年第28卷第1期,共21页

基　　金：We thank Prof Qishui Lin (SIBCB, CAS) for invaluable ad- vice. We appreciate Drs Xiang Yu, Jiulin Du, Bo Yuan (Institute of Neuroscience, SIBS, CAS), Donghong Cui, Han Li (Shanghai Mental Health Center) for providing technical assistance, and Zi Li (Institute of Nutritional Sciences, SIBS, CAS) for technical help in HPLC-MS/MS. We specially acknowledge the excel- lent support from proteomics facility at the National Center for Protein Science Shanghai, and the cell imaging center led by Dr Wei Bian at SIBCB. We thank all members of our laboratory for support and Ms Yalan Wu for assistance. We are also grateful to Dr ZeNan Chang (University of California, Los Angeles) for critical reading of the manuscript. This work was supported bythe Strategic Priority Research Program of the Chinese Academy of Sciences (XDB19000000 and XDA12040323), the National Natural Science Foundation of China (31470770 and 81525019 to Rtt; 81601203 to XX; 81330027 and 81525007 to KX; 31400919 and 31671114 to HG), the Ministry of Science and Technology of China (2013CB910900 to RH) and the China Postdoctoral Science Foundation (2016M591724 to XX). 摘　　要：孤独性光谱混乱(ASD ) 是有异构的病原学的许多人的神经病学的混乱。E3 ubiquitin (Ub ) 的活动过度 ligase UBE3A,不完全地源自 15q11-q13 拷贝数字变化,为世界范围的 ASD 盒子的 1%-3% 的报道,而是内在的机制遗体描绘了。这里,我们报导 ALDH1A2 的功能, retinoic 酸(RA ) 的限制率的酶合成,被 UBE3A 否定地以一种 ubiquitylation 依赖的方式调整。过多的 UBE3A 剂量被发现损害调停 RA 的 neuronal homeostatic synaptic 粘性。象 ASD 一样症状被 overexpressing UBE3A 在前额的外皮或由一个 ALDH1A 对手的管理在老鼠概括,而 RA 补充显著地减轻了过多的 UBE3A 导致剂量的象 ASD 一样显型。由识别在 ASD 作为内在的机制发信号的减少的 RA,显型连接了到 UBE3A 活动过度,我们的调查结果介绍 ASD 病原学的新远景并且对这逐渐地流行的疾病便于治疗学的开发的一个模式。

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Excessive UBE3A dosage impairs retinoic acid signaling and synaptic plasticity in autism spectrum disorders

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