The dynamics of rapsyn in vitro and in vivo

rapsyn 的体外和体内动力学

• 批准号: 7157995
• 负责人: EMILE G BRUNEAU
• 金额: $ 3.25万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-05 至 2008-08-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7157995
• 关键词: proteins; receptor; synapses

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.

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 是唯一已知可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，例如 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 已知对受体聚集和突触形成至关重要，因为敲除小鼠中的 rapsyn 是致命的，而 rapsyn 基因或启动子中的单点突变能够导致人类严重的肌营养不良症。由于 rapsyn 与 AChR 密切相关，并且对于正确的受体定位至关重要，因此了解与 AChR 相比的 rapsyn 动力学和运输将非常有意义。这些研究的结果还可能帮助我们更好地理解在不易接近的中央突触处参与突触可塑性的类似蛋白质的动态。此外，许多神经肌肉疾病呈现突触后支架蛋白的改变。因此，通过研究这些蛋白质的行为，我们也许能够确定开发神经肌肉疾病疗法的新途径。