Goldman D, Sapru M K
Mental Health Research Institute, University of Michigan, Ann Arbor 48109, USA.
Can J Appl Physiol. 1998 Aug;23(4):390-5. doi: 10.1139/h98-023.
Adult skeletal muscle locally expresses nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction by selective induction of their subunit-encoding genes (alpha beta epsilon delta) in endplate-associated myonuclei. Neuregulin/ARIA is a nerve-derived factor that is thought to be largely responsible for this local gene induction. Neuregulin/ARIA activates a Ras/MAP kinase signalling cascade, which ultimately induces nAChR epsilon-subunit gene expression via a 15 bp sequence that harbors a core Ets transcription factor binding site (GGA). Interestingly, this same sequence also appears to participate in extrajunctional repression of the epsilon-subunit gene. Muscle Ets 2 overexpression induces nAChR epsilon-subunit gene promoter activity, whereas a dominant/negative Ets blocks neuregulin-dependent induction. These results suggest that Ets transcription factors play a role in mediating synapse-specific and neuregulin-mediated motor neuron control of nAChR gene expression.
成年骨骼肌通过在终板相关肌细胞核中选择性诱导烟碱型乙酰胆碱受体（nAChRs）的亚基编码基因（α、β、ε、δ），在神经肌肉接头处局部表达nAChRs。神经调节蛋白/ARIA是一种神经源性因子，被认为在很大程度上负责这种局部基因诱导。神经调节蛋白/ARIA激活Ras/丝裂原活化蛋白激酶信号级联反应，最终通过一个包含核心Ets转录因子结合位点（GGA）的15bp序列诱导nAChR ε亚基基因表达。有趣的是，相同的序列似乎也参与ε亚基基因的接头外抑制。肌肉Ets 2的过表达诱导nAChR ε亚基基因启动子活性，而显性/阴性Ets则阻断神经调节蛋白依赖性诱导。这些结果表明，Ets转录因子在介导nAChR基因表达的突触特异性和神经调节蛋白介导的运动神经元控制中发挥作用。
