Stimulation of acetylcholine receptor transcription by neuregulin-2 requires an N-box response element and is regulated by alternative splicing.
Stimulation of acetylcholine receptor transcription by neuregulin-2 requires an N-box response element and is regulated by alternative splicing.
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神经调节蛋白-2 刺激乙酰胆碱受体转录需要 N 盒反应元件，并受到选择性剪接的调节。
DOI：
10.1016/j.neuroscience.2005.04.028
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Rimer,M
中科院分区：
文献类型：
--
作者：
Ponomareva,ON;Ma,H;Dakour,R;Raabe,TD;Lai,C;Rimer,M
生长/分化因子的神经调节蛋白（Nrg）家族由哺乳动物基因组中的至少四个基因编码：nrg-1、nrg-2、nrg-3和nrg-4。Nrg-1和Nrg-2在该家族中具有最高的同源性，并且来自其编码基因的初级RNA转录物经受广泛的选择性剪接。虽然对Nrg-2-4的生物学功能知之甚少，但它们与Nrg-1的结构相似性表明它们可以解释目前归因于Nrg-1的一些活性。因此，在神经肌肉接头处，Nrg-1是激活突触肌核中选择性乙酰胆碱受体（AChR）转录的信号的有利候选者。然而，我们最近发现，像Nrg-1，Nrg-2也可以激活AChR的转录在培养的肌管和积累在突触部位。突触特异性和Nrg-1诱导的AChR转录需要一个增强子序列，即N-box，该序列在一些先天性重症肌无力患者中也发生突变。在这里，我们表明，NRG-2诱导AChR转录需要一个N盒基序，并通过选择性剪接调节。我们还表明，独特的Nrg-2亚型的差异分布在脊髓和骨骼肌，该组织的神经肌肉突触的细胞成分的港口。
The neuregulin (Nrg) family of growth/differentiation factors is encoded by at least four genes in the mammalian genome: nrg-1, nrg-2, nrg-3 and nrg-4. Nrg-1 and Nrg-2 share the highest homology within the family, and the primary RNA transcripts from their encoding genes are subjected to extensive alternative splicing. Although little is known about the biological function of Nrg-2-4, their structural similarity with Nrg-1 suggests that they could account for some of the activities presently attributed to Nrg-1. Thus, at the neuromuscular junction Nrg-1 has been a favored candidate for the signal that activates selective acetylcholine receptor (AChR) transcription in synaptic myonuclei. However, we have recently shown that like Nrg-1, Nrg-2 can also activate AChR transcription in cultured myotubes and accumulates at the synaptic site. Synapse-specific and Nrg-1-induced AChR transcription require an enhancer sequence, the N-box, which is also mutated in some patients with congenital myasthenia gravis. Here, we show that Nrg-2-induced AChR transcription requires an N-box motif and is regulated by alternative splicing. We also show that unique Nrg-2 isoforms are differentially distributed between spinal cord and skeletal muscle, the tissues that harbor the cellular components of the neuromuscular synapse.