NEUREGULIN SIGNALLING AT THE NEUROMUSCULAR SYNAPSE

突触的形成需要协调合成和定位 一组独特的分子。在神经肌肉发育过程中 在连接处，肌肉合成了许多特殊的蛋白质 细胞，并定位于突触区域。这其中的一个 其主要成分是乙酰胆碱受体(AchR)。其中一种机制是 负责定位ACHR的是通过将转录限制在一个 突触区域的肌纤维核的亚群。这个突触- 特异性基因表达被认为是由神经调节蛋白诱导的，这是一种因子 它存在于运动神经元中。在培养的肌肉细胞中，中性调节蛋白 可以诱导ACHR基因的转录，为 分析这一信号通路。在拟议的实验中，直接 神经调节蛋白信号通路与A基因启动子的相互作用 反应基因，ACHR epsilon亚单位基因，将被检测。这个 本研究的具体目的是：1)确定ACHR中的要素 与中性调节蛋白诱导有关的Epsilon启动子 表达和突触特异性基因表达，以及2)识别 与NRG反应元件相互作用的蛋白质 推动者。除了提供有关发展的信息 神经肌肉突触，拟议的实验也可能产生洞察力 到其他受NeuRegin信号影响的过程中，如 作为细胞转化。

Synapse formation requires the coordinated synthesis and localization of a unique set of molecules. During development of the neuromuscular junction, a number of specialized proteins are synthesized by muscle cells and localized specifically at synaptic regions. One of these components is the acetylcholine receptor (AchR). One of the mechanisms responsible for localizing the AchR is by restricted transcription to a subset of muscle fiber nuclei at the synaptic region. This synapse- specific gene expression is thought to be induced by neuregulin, a factor which is present in motor neurons. In cultured muscle cells, neuregulin can induce transcription of AchR genes, providing a useful system for analyzing this signaling pathway. In the proposed experiments, the direct interaction of the neuregulin signaling pathway with the promoter of a responsive gene, the AchR epsilon subunit gene, will be examined. The specific aims of this research are 1) to identify elements in the AchR epsilon promoter which are responsible for neuregulin-inducible expression and for synapse-specific gene expression, and 2) To identify proteins that interact with NRG-response elements in the epsilon promoter. In addition to providing information on development of the neuromuscular synapse, the proposed experiments may also yield insight into other processes which are influenced by neuregulin signaling, such as cellular transformation.