The dynamics of rapsyn in vitro and in vivo

描述(由申请人提供)：这项研究的主要目的是确定乙酰胆碱受体相关蛋白Rapsyn的动力学和细胞内转运。Rapsyn是已知的唯一直接与乙酰胆碱受体结合的细胞内蛋白，并且在功能上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)和吉菲林(与甘氨酸和GABA受体结合)。Rapsyn对受体聚集和突触形成至关重要，因为Rapsyn在小鼠中的敲除是致命的，Rapsyn基因或启动子的单点突变能够导致人类严重的肌肉营养不良。由于Rapsyn与AChRs密切相关，并对受体的正确定位至关重要，因此了解Rapsyn的动力学和与AChRs相比的贩运将是非常有意义的。这些研究的结果也可能帮助我们更好地理解类似蛋白的动力学，这些蛋白参与了较难到达的中央突触的突触可塑性。此外，许多神经肌肉疾病表现为突触后支架蛋白的改变。因此，通过研究这些蛋白质的行为，我们可能能够确定开发神经肌肉疾病治疗的新途径。

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.