NEUREGULIN SIGNALLING AT THE NEUROMUSCULAR SYNAPSE

突触的形成需要协调的合成和定位 一组独特的分子在神经肌肉的发育过程中， 在连接处，肌肉合成许多专门的蛋白质 细胞，并专门定位于突触区域。其中一 乙酰胆碱受体（AchR）。的机制之一 负责定位AchR的是通过限制性转录到 在突触区域的肌纤维核的子集。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， 存在于运动神经元中。在培养的肌肉细胞中， 可以诱导AchR基因的转录，提供了一个有用的系统， 分析这个信号通路。在所提出的实验中， 神经调节蛋白信号传导途径与一个 将检测AchR β亚基基因。的 本研究的具体目的是：1）识别AchR中的元素 启动子，负责神经调节蛋白诱导的 表达和突触特异性基因表达，以及2）鉴定 与NRG反应元件相互作用的蛋白质 启动子除了提供关于发展 神经肌肉突触，拟议的实验也可能产生洞察力 神经调节蛋白信号影响的其他过程， as cellular细胞transformation转换.

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.