Wnt/beta-catenin signaling suppresses Rapsyn expression and inhibits acetylcholine receptor clustering at the neuromuscular junction

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	Wnt/beta-catenin signaling suppresses Rapsyn expression and inhibits acetylcholine receptor clustering at the neuromuscular junction
	Luo, Zhen-Ge
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2008
卷号	283 期号:31 页码:21668-21675
关键词	BETA-CATENIN SYNAPSE FORMATION POSTSYNAPTIC DIFFERENTIATION AXON GUIDANCE WNT PROTEIN MUSCLE KINASE TRANSCRIPTION NEUROTRANSMITTER
ISSN号	0021-9258
通讯作者	Luo, ZG (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Neurosci, Inst Neurosci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China,zgluo@ion.ac.cn
英文摘要	The dynamic interaction between positive and negative signals is necessary for remodeling of postsynaptic structures at the neuromuscular junction. Here we report that Wnt3a negatively regulates acetylcholine receptor ( AChR) clustering by repressing the expression of Rapsyn, an AChR-associated protein essential for AChR clustering. In cultured myotubes, treatment with Wnt3a or overexpression of beta-catenin, the condition mimicking the activation of the Wnt canonical pathway, inhibited Agrin-induced formation of AChR clusters. Moreover, Wnt3a treatment promoted dispersion of AChR clusters, and this effect was prevented by DKK1, an antagonist of the Wnt canonical pathway. Next, we investigated possible mechanisms underlying Wnt3a regulation of AChR clustering in cultured muscle cells. Interestingly, we found that Wnt3a treatment caused a decrease in the protein level of Rapsyn. In addition, Rapsyn promoter activity in cultured muscle cells was inhibited by the treatment with Wnt3a or beta-catenin overexpression. Forced expression of Rapsyn driven by a promoter that is not responsive to Wnt3a prevented the dispersing effect of Wnt3a on AChR clusters, suggesting that Wnt3a indeed acts to disperse AChR clusters by down-regulating the expression of Rapsyn. The role of Wnt/beta-catenin signaling in dispersing AChR clusters was also investigated in vivo by electroporation of Wnt3a or beta-catenin into mouse limb muscles, where ectopic Wnt3a or beta-catenin caused disassembly of postsynaptic apparatus. Together, these results suggest that Wnt/beta-catenin signaling plays a negative role for postsynaptic differentiation at the neuromuscular junction, probably by regulating the expression of synaptic proteins, such as Rapsyn.
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/331001/1706]
专题	上海神经科学研究所_神经所(总) 上海神经科学研究所_突触信号研究组
推荐引用方式 GB/T 7714	Luo, Zhen-Ge. Wnt/beta-catenin signaling suppresses Rapsyn expression and inhibits acetylcholine receptor clustering at the neuromuscular junction[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2008,283(31):21668-21675.
APA	Luo, Zhen-Ge.(2008).Wnt/beta-catenin signaling suppresses Rapsyn expression and inhibits acetylcholine receptor clustering at the neuromuscular junction.JOURNAL OF BIOLOGICAL CHEMISTRY,283(31),21668-21675.
MLA	Luo, Zhen-Ge."Wnt/beta-catenin signaling suppresses Rapsyn expression and inhibits acetylcholine receptor clustering at the neuromuscular junction".JOURNAL OF BIOLOGICAL CHEMISTRY 283.31(2008):21668-21675.