The neuromuscular junction (nmj) is used as a model synapse to study an important aspect of synaptic regulation. The innervated adult nmj is a very stable synapse both morphologically and metabolically. Changes are constantly occurring during development and during aging, but its integrity is maintained to a large extent by neural innervation. A longterm aim of this proposal is to understand how the nerve maintains the structure and function of a stable nmj. One manifestation of the junctional stability is the presence of acetylcholine receptors (AChRs) at a very high density and slow degradation rate (t 1/2 about 10 days). It is well known that during development or in the reinnervation of a denervated nmj there is a replacement of a rapidly degrading, gamma subunit-containing, AChR population (Rr), by a slowly degrading epsilon subunit-containing, AChR population (Rs).
The specific aims of this research are i) to test hypotheses regarding the possible stages in producing and maintaining nmj stability, ii) to establish the role played by, the AChR subunit composition, and phosphorylation of the epsilon subunit, and iii) to identify neural factors and cytoskeletal elements involved in establishing AChR stability. The role of the two AChR populations (Rr and Rs), differing in degradation properties, will be assessed. Studies will involve electron microscope autoradiography and immunocytochemistry, in vivo studies, in vitro tissue and organ culture preparations and molecular approaches.
