The dynamics of rapsyn in vitro and in vivo

描述（由申请人提供）：本研究的主要目的是确定乙酰胆碱受体相关蛋白rapsyn的动力学和细胞内运输。Rapsyn是已知的唯一直接与乙酰胆碱受体结合的细胞内蛋白，其功能类似于许多其他受体相关蛋白，如PSD-95（与NMDA受体结合），GRIP（与AMPA受体结合）和gephyrin（与甘氨酸和GABA受体结合）。Rapsyn对于受体聚集和突触形成至关重要，因为在小鼠中敲除Rapsyn是致命的，Rapsyn基因或启动子的单点突变能够导致人类严重的肌肉萎缩症。由于rapsyn与achr密切相关，并且对受体的适当定位至关重要，因此与achr相比，了解rapsyn的动态和运输将是非常有趣的。这些研究的结果也可以帮助我们更好地理解在不易接近的中枢突触中参与突触可塑性的类似蛋白质的动力学。此外，许多神经肌肉疾病表现为突触后支架蛋白的改变。通过研究这些蛋白质的行为，我们可能因此能够为神经肌肉疾病的治疗方法的发展确定新的途径。

DESCRIPTION (provided by applicant): The main objective of this study is to determine the dynamics and intracellular trafficking of the acetylcholine receptor associated protein, rapsyn. Rapsyn is the only intracellular protein known to bind directly to acetylcholine receptors, and is functionally analogous to a number of other receptor associated proteins such as PSD-95 (which binds to NMDA receptors), GRIP (which binds to AMPA receptors) and gephyrin (which binds to glycine and GABA receptors). Rapsyn is known to be essential to receptor clustering and synapse formation, as knockouts of rapsyn in mice are lethal, and single point mutations in the rapsyn gene or promoter are able to cause severe muscular dystrophies in humans. Since rapsyn is intimately associated with AChRs and is crucial for proper receptor localization, it will be of great interest to gain an understanding of rapsyn dynamics and trafficking in comparison to AChRs. The results of these studies may also help us to better understand the dynamics of analogous proteins that are involved in synaptic plasticity at less accessible central synapses. In addition, many neuromuscular diseases present alterations in post-synaptic scaffolding proteins. By investigating the behavior of these proteins we may therefore be able to define new avenues for the development of therapies for neuromuscular disease.