8月19日,，《神經(jīng)科學(xué)雜志》（The Journal of Neuroscience）發(fā)表了中國科學(xué)院上海生命科學(xué)研究院神經(jīng)科學(xué)研究所的研究成果：“NFkappaB控制乙酰膽堿受體在神經(jīng)肌肉接頭的聚集”。該項工作是由王佳和伏秀清等在羅振革研究員指導(dǎo)下完成的,。
轉(zhuǎn)錄因子NFkB在炎癥和免疫反應(yīng)中起重要的調(diào)控作用,，但在神經(jīng)系統(tǒng)的功能尚不清楚。羅振革研究員帶領(lǐng)的突觸信號研究組分析了NFkB在神經(jīng)肌肉接頭突觸形成中的作用,。首先,，他們發(fā)現(xiàn)NFkB的p65亞基在神經(jīng)肌肉接頭部位存在富集。在培養(yǎng)的肌肉細胞上調(diào)p65的表達促進了乙酰膽堿受體的聚集,。相反,，下調(diào)p65的表達或抑制NFkB的功能抑制了乙酰膽堿受體聚集體的形成。在骨骼肌中特異地敲除p65基因可導(dǎo)致小鼠神經(jīng)肌肉接頭的發(fā)育異常,。
通過分析p65的作用機制,，他們發(fā)現(xiàn)p65對突觸部位腳手架蛋白Rapsyn的表達起重要的調(diào)節(jié)作用。因此,，炎性因子NFkB介導(dǎo)的轉(zhuǎn)錄調(diào)控在神經(jīng)肌肉接頭突觸形成中發(fā)揮重要的作用,。
該工作得到了中國科學(xué)院、國家科技部,、自然科學(xué)基金委及上海市科委的資助,。（生物谷Bioon.com）
生物谷推薦原文出處：
The Journal of Neuroscience doi:10.1523/JNEUROSCI.2118-10.2010
Nuclear Factor B Controls Acetylcholine Receptor Clustering at the Neuromuscular Junction
Jia Wang, * Xiu-Qing Fu, * Wen-Liang Lei, Tong Wang, Ai-Li Sheng, and Zhen-Ge Luo
Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
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 B (NF-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-B or inhibiting NF-B activity by overexpression of mutated form of IB (inhibitor B), which is resistant to proteolytic degradation and thus constitutively keeps NF-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-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-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-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-B signaling controls AChR clustering through transcriptional regulation of synaptic protein Rapsyn.
