Formation and maintenance of the neuromuscular junction (NMJ) involves the coordinated regulation of gene expression, post-translational processing, assembly of supramolecular protein complexes and protein degradation of a number of specific components. Until recently, the nicotinic acetylcholine receptor (AChR) served as the primary and certainly best studied example of a specific component of the NMJ. Indeed, studies of AChR have led to a firm appreciation of the importance of the delicate balance of synthetic and degradative processes that maintain this synapse. The clinical symptoms of autoimmune, as well as some co genital types of myasthenia gravis, can be understood in terms of their effects on the site-density of AChR at the synapse. In the past several years, monoclonal antibody and recombinant DNA reagents have become available for. the neural cell adhesion molecule (N-CAM), the 43 kDa receptor associated protein (RAPsyn), the junction specific basal lamina component (JS-1) and acetylcholinesterase (AChE); all are interesting and unique components of the NMJ in their own right. Here, we propose to characterize the basic mechanisms involved in the post-translational processing, assembly and stabilization of the AChR, RAPsyn and JS-l molecules. Also, we will study the mechanisms responsible for synapse specific transcriptional regulation of the embryonic (alpha, beta, gamma, and delta) and adult (epsilon) subunits of the AChR as well as RAPsyn, JS-1 and AChE. We will employ DNA mediated gene transfer and transgenic animal techniques for these studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019910-11
Application #
3400040
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1983-01-01
Project End
1996-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
11
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130