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. ? ?
| Bruneau, Emile G; Brenner, Daniel S; Kuwada, John Y et al. (2008) Acetylcholine receptor clustering is required for the accumulation and maintenance of scaffolding proteins. Curr Biol 18:109-15 |
| Bruneau, Emile; Akaaboune, Mohammed (2007) The dynamics of the rapsyn scaffolding protein at individual acetylcholine receptor clusters. J Biol Chem 282:9932-40 |
