Role of Ab1/Arg Kinases in the Formation of the NMJ

描述(由申请人提供)：神经肌肉连接的发展和维持--神经和肌肉交流的地方--对我们的正常功能至关重要。这一领域的研究对重症肌无力等神经肌肉疾病有明显的影响，但也提供了关于神经回路形成方式的关键信息。NMJ和其他突触的突触前和突触后信号导致受体聚集和加强连接，从原本相当于一根缠绕的电线的地方创造出有意义的电路。这个项目研究了导致突触后肌肉细胞中乙酰胆碱受体聚集的信号级联。具体地说，我们试图确定集聚蛋白刺激与非受体Abl酪氨酸激酶活性相联系的方法。我们将确定集聚蛋白刺激是否导致Abl活性增加，并促进与集聚蛋白受体穆斯克的联系。我们还将阐明Abl介导受体聚集的机制，包括研究Abl的活性是否部分由Rapsyn介导，Rapsyn是一种已知直接影响受体聚集的蛋白质。

DESCRIPTION (provided by applicant): The development and maintenance of the neuromuscular junction - the place where nerve and muscle communicate - is critical to our proper functioning. Research in this area has obvious implications for neuromuscular disorders such as myasthenia gravis, but also provides crucial information about the way that neural circuits are formed. Pre- and post-synaptic signals at the NMJ and other synapses lead to receptor clustering and strengthened connections, creating meaningful circuitry from what would otherwise be the equivalent of a tangle of wires. This project investigates the signaling cascade that leads to acetylcholine receptor clustering in the post-synaptic muscle cell. Specifically, we seek to define the means by which agrin stimulation is linked to non-receptor Abl tyrosine kinase activity. We will determine whether agrin stimulation leads to increased Abl activity and promotes association with the agrin receptor MUSK. We will also elucidate the mechanisms by which Abl mediates receptor clustering, including an investigation of whether Abl activity is partially mediated by Rapsyn, a protein known to directly affect receptor clustering.