Nuclear Factor kappa B Controls Acetylcholine Receptor Clustering at the Neuromuscular Junction

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	Nuclear Factor kappa B Controls Acetylcholine Receptor Clustering at the Neuromuscular Junction
	Luo, Zhen-Ge
刊名	JOURNAL OF NEUROSCIENCE
	2010
卷号	30 期号:33 页码:11104-11113
关键词	RAPSYN-DEFICIENT MICE SYNAPSE FORMATION TYROSINE PHOSPHORYLATION TRANSCRIPTION FACTOR TRANSGENIC MICE MUSCLE-CELLS EXPRESSION AGRIN MUSK PROTEIN
ISSN号	0270-6474
通讯作者	Luo, ZG (reprint author), Chinese Acad Sci, Inst Neurosci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China,zgluo@ion.ac.cn
英文摘要	At the vertebrate neuromuscular junction (NMJ), acetylcholine receptor (AChR) clustering is stimulated by motor neuron-derived glycoprotein Agrin and requires a number of intracellular signal or structural proteins, including AChR-associated scaffold protein Rapsyn. Here, we report a role of nuclear factor kappa B (NF-kappa B), a well known transcription factor involved in a variety of immune responses, in regulating AChR clustering at the NMJ. We found that downregulating the expression of RelA/p65 subunit of NF-kappa B or inhibiting NF-kappa B activity by overexpression of mutated form of I kappa B (inhibitor kappa B), which is resistant to proteolytic degradation and thus constitutively keeps NF-kappa B inactive in the cytoplasma, impeded the formation of AChR clusters in cultured C2C12 muscle cells stimulated by Agrin. In contrast, overexpression of RelA/p65 promoted AChR clustering. Furthermore, we investigated the mechanism by which NF-kappa B regulates AChR clustering. Interestingly, we found that downregulating the expression of RelA/p65 caused a marked reduction in the protein and mRNA level of Rapsyn and upregulation of RelA/p65 enhanced Rapsyn promoter activity. Mutation of NF-kappa B binding site on Rapsyn promoter prevented responsiveness to RelA/p65 regulation. Moreover, forced expression of Rapsyn in RelA/p65 downregulated muscle cells partially rescued AChR clusters, suggesting that NF-kappa B regulates AChR clustering, at least partially through the transcriptional regulation of Rapsyn. In line with this notion, genetic ablation of RelA/p65 selectively in the skeletal muscle caused a reduction of AChR density at the NMJ and a decrease in the level of Rapsyn. Thus, NF-kappa B signaling controls AChR clustering through transcriptional regulation of synaptic protein Rapsyn.
学科主题	Neurosciences & Neurology
收录类别	SCI
资助信息	National Natural Science Foundation of China[30721004, 30825013]; National Basic Research Program[2006CB806600, 2011CB809002]; Key State Research Program of China[2006CB943900]; Chinese Academy of Sciences[KSCX2-YW-R-102]; Program of Shanghai Subject Chief Scientist[08XD14050]
语种	英语
公开日期	2012-07-13
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1580]
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. Nuclear Factor kappa B Controls Acetylcholine Receptor Clustering at the Neuromuscular Junction[J]. JOURNAL OF NEUROSCIENCE,2010,30(33):11104-11113.
APA	Luo, Zhen-Ge.(2010).Nuclear Factor kappa B Controls Acetylcholine Receptor Clustering at the Neuromuscular Junction.JOURNAL OF NEUROSCIENCE,30(33),11104-11113.
MLA	Luo, Zhen-Ge."Nuclear Factor kappa B Controls Acetylcholine Receptor Clustering at the Neuromuscular Junction".JOURNAL OF NEUROSCIENCE 30.33(2010):11104-11113.