REGULATION OF THE ACETYLCHOLINE-RECEPTOR EPSILON-SUBUNIT GENE BY RECOMBINANT ARIA - AN IN-VITRO MODEL FOR TRANSYNAPTIC GENE-REGULATION
REGULATION OF THE ACETYLCHOLINE-RECEPTOR EPSILON-SUBUNIT GENE BY RECOMBINANT ARIA - AN IN-VITRO MODEL FOR TRANSYNAPTIC GENE-REGULATION
复制标题
DOI：
10.1016/0896-6273(95)90289-9
复制
发表时间：
1995-02-01
期刊：
影响因子：
16.2
通讯作者：
MERLIE, JP
中科院分区：
文献类型：
--
作者：
CHU, GC;MOSCOSO, LM;MERLIE, JP
突触后骨骼肌膜的结构特化部分是由运动神经元诱导的突触肌核转录调节介导的。ARIA是一种刺激乙酰胆碱受体（AChR）产生的因子，是这种调节的候选信号分子。在这里，我们研究这种多肽因子的跨突触诱导潜力。ARIA免疫反应性可在体内突触部位检测到。在体外，重组heregulin β 1（rHRG β 1），ARIA的人类同源物，诱导AChR β基因的表达，AChR β基因是对突触输入最敏感的亚基。rHRG β 1的诱导特性在来自携带启动子-核lacZ报告基因转基因的转基因小鼠的原代肌肉培养物中得到最显著的证明。瞬时转染实验;使用Sol 8肌肉细胞系的结果表明，赋予对ARIA的应答性的序列位于150 bp的ARIA亚基启动子区域内，并且是E盒非依赖性的。这些结果表明，ARIA通过指导神经肌肉接头处的空间限制基因表达来发挥重要作用。
Structural specialization of the postsynaptic skeletal muscle membrane is in part mediated by the motor neuron-induced transcriptional regulation of synaptic muscle nuclei. ARIA, a factor that stimulates production of acetylcholine receptors (AChRs), is a candidate signaling molecule for such regulation. Here we examine the transynaptic inducing potential of this polypeptide factor. ARIA immunoreactivity is detectable at synaptic sites in vivo. In vitro, recombinant heregulin beta 1 (rHRG beta 1), the human homolog of ARIA, induces expression of the AChR epsilon gene, the subunit most sensitive to synaptic input. The inducing property of rHRG beta 1 is demonstrated most dramatically in primary muscle cultures from transgenic mice bearing an epsilon promoter-nuclear lacZ reporter transgene. transient transfection experiment; using the Sol 8 muscle cell line indicate that sequences that confer responsiveness to ARIA are located within a 150 bp epsilon subunit promoter region and are, E box-independent. These results suggest that ARIA performs a vital role by directing spatially restricted gene expression at the neuromuscular junction.