Angelman Syndrome Protein Ube3a Regulates Synaptic Growth and Endocytosis by Inhibiting BMP Signaling in Drosophila

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	Angelman Syndrome Protein Ube3a Regulates Synaptic Growth and Endocytosis by Inhibiting BMP Signaling in Drosophila
	Li, WH; Yao, AY; Zhi, H; Kaur, K; Zhu, YC; Jia, MY; Zhao, H; Wang, QF; Jin, S; Zhao, GL
刊名	PLOS GENETICS
	2016
卷号	12 期号:5 页码:e1006062
关键词	E3 UBIQUITIN LIGASE NEUROMUSCULAR-JUNCTION TRANSCRIPTION FACTOR RETROGRADE SIGNAL NERVOUS-SYSTEM MOUSE MODEL GENE UBE3A EXPRESSION MAD DEGRADATION
通讯作者	Yao, AY ; Zhang, YQ (reprint author), Chinese Acad Sci, Inst Genet & Dev Biol, Key Lab Mol & Dev Biol, Beijing, Peoples R China.,ayyao@genetics.ac.cn ; yqzhang@genetics.ac.cn
英文摘要	Altered expression of the E3 ubiquitin ligase UBE3A, which is involved in protein degradation through the proteasome-mediated pathway, is associated with neurodevelopmental and behavioral defects observed in Angelman syndrome (AS) and autism. However, little is known about the neuronal function of UBE3A and the pathogenesis of UBE3A-associated disorders. To understand the in vivo function of UBE3A in the nervous system, we generated multiple mutations of ube3a, the Drosophila ortholog of UBE3A. We found a significantly increased number of total boutons and satellite boutons in conjunction with compromised endocytosis in the neuromuscular junctions (NMJs) of ube3a mutants compared to the wild type. Genetic and biochemical analysis showed upregulation of bone morphogenetic protein (BMP) signaling in the nervous system of ube3a mutants. An immunochemical study revealed a specific increase in the protein level of Thickveins (Tkv), a type I BMP receptor, but not other BMP receptors Wishful thinking (Wit) and Saxophone (Sax), in ube3a mutants. Ube3a was associated with and specifically ubiquitinated lysine 227 within the cytoplasmic tail of Tkv, and promoted its proteasomal degradation in Schneider 2 cells. Negative regulation of Tkv by Ube3a was conserved in mammalian cells. These results reveal a critical role for Ube3a in regulating NMJ synapse development by repressing BMP signaling. This study sheds new light onto the neuronal functions of UBE3A and provides novel perspectives for understanding the pathogenesis of UBE3A-associated disorders.
学科主题	Genetics & Heredity
WOS标题词	Genetics & Heredity
语种	英语
WOS记录号	WOS:000377197100060
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/4023]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Li, WH,Yao, AY,Zhi, H,et al. Angelman Syndrome Protein Ube3a Regulates Synaptic Growth and Endocytosis by Inhibiting BMP Signaling in Drosophila[J]. PLOS GENETICS,2016,12(5):e1006062.
APA	Li, WH.,Yao, AY.,Zhi, H.,Kaur, K.,Zhu, YC.,...&Zhang, YQ.(2016).Angelman Syndrome Protein Ube3a Regulates Synaptic Growth and Endocytosis by Inhibiting BMP Signaling in Drosophila.PLOS GENETICS,12(5),e1006062.
MLA	Li, WH,et al."Angelman Syndrome Protein Ube3a Regulates Synaptic Growth and Endocytosis by Inhibiting BMP Signaling in Drosophila".PLOS GENETICS 12.5(2016):e1006062.