突触是神经元之间或者神经元和效应细胞之间传递信号的最基本的功能单位，是形成神经环路的基础。神经肌肉接头（Neuromuscular junction，NMJ）是连接运动神经元和骨骼肌的突触，控制着身体的运动和呼吸。虽然已经发现了一些NMJ形成的重要蛋白，但是还有更多的蛋白有待发现，关于NMJ形成的分子机制尚需深入研究。本项目将从NMJ的关键蛋白Lrp4入手，利用特异在肌肉组织中表达Flag-Lrp4的转基因小鼠，采用免疫沉淀结合质谱的方法分别从突触前和突触后在体探寻参与NMJ形成的新的蛋白分子。并且研究这些蛋白在发育过程中对突触前和突触后分化的作用，以及成年后在NMJ维持中发挥的功能。本研究将帮助深入理解NMJ形成和维持的分子机制，为相关人类疾病的诊断和治疗提供新的靶点和思路。

Synapses are fundamental units of neuronal circuitry in the nervous system that enable communications between neurons and between neuron and its target cell. The neuromuscular junction (NMJ) is a synapse between motor neurons and skeleton muscles, controlling muscle contraction and breathing. Although many key proteins in NMJ formation have been identified, more novel proteins should be explored. The mechanisms of how proteins are assembled to form functional synapses need to be further investigated. Here, we conduct unbiased IP-MS screens to identify Lrp4-binding proteins in both pre- and post-synaptic regions. The function of candidates will be studied in both pre- and post-synaptic differentiation during development and in NMJ maintenance during adulthood. Our research will provide a better understanding of molecular mechanisms of NMJ formation and maintenance and contribute to new diagnostic and therapeutic strategies for the neuromuscular disorders.