Activity of the nicotinic acetylcholine receptor α5 and α7 subunit promoters in muscle cells
Activity of the nicotinic acetylcholine receptor α5 and α7 subunit promoters in muscle cells
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DOI：
10.1089/104454901753340640
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发表时间：
2001-10-01
影响因子：
3.1
通讯作者：
Criado, M
中科院分区：
文献类型：
--
作者：
Campos-Caro, A;Carrasco-Serrano, C;Criado, M
乙酰胆碱受体α 5和α 7亚基是在神经系统中表达的不同烟碱受体亚型的组分。然而，它们也存在于非神经元组织中。我们在小鼠C2C12肌细胞中检测到了α 5和α 7转录本。此外，在成肌细胞分化成肌管时，α 7转录物的量显著增加，而α 5保持不变。为了探索这些神经元基因的表达是如何在肌肉中调节的，我们已经表征了它们的启动子活性。对转染报告基因的缺失和突变分析表明，转录活性受到在神经元样细胞中也起作用的调节元件的控制。因此，α 5亚基核心启动子的活性降低到接近50%的一个，两个或三个的五个Sp1结合位点的改变存在于该区域，几乎被废除时，四个或五个位点同时突变。在α 7亚基启动子的情况下，上游刺激因子和早期生长反应基因转录因子参与调节其转录活性。此外，在分化过程中，alpha7启动子被激活，其机制部分依赖于上述因素。
The acetylcholine receptor alpha5 and alpha7 subunits are components of different nicotinic receptor subtypes expressed in the nervous system. However, they are also present in non-neuronal tissues. We have detected alpha5 and alpha7 transcripts in mouse C2C12 muscle cells. Moreover, on differentiation of myoblasts into myotubes, the amount of alpha7 transcripts increased significantly, whereas alpha5 remained unchanged. In order to explore how the expression of these neuronal genes is regulated in muscle, we have characterized their promoter activities. Deletion and mutagenesis analysis with transfected reporter genes showed that transcriptional activity was controlled by regulatory elements also operative in neuronal-like cells. Thus, the activity of the alpha5 subunit core promoter decreased to similar to 50% on alteration of one, two, or three of the five Sp1 binding sites present in this region and was almost abolished when four or five sites were mutated simultaneously. In the case of the alpha7 subunit promoter, the upstream stimulatory factor and the early growth response gene transcription factor were involved in regulating its transcriptional activity. In addition, the alpha7 promoter was activated during the differentiation process, in a mechanism partially dependent on the mentioned factors.