Experiments are proposed which will determine mechanisms governing synthesis and assembly of acetylcholine receptor. The nicotinic ACh-receptor is an integral membrane glycoprotein of muscle which binds Ach released by the nerve. The mechanism by which ACh binding results in a change in membrane permeability culminating in muscle contraction is under intensive study in a number of laboratories. Mechanisms governing receptor synthesis and destruction also deserve intensive study because they are important to the overall function of AChR during development, disease, and regeneration. The synthesis of ACh-receptor as well as other specific proteins is regulated by nerve induced muscle activity. My goal is to study the regulation of synthesis and assembly of the ACh-receptor at the molecular and cellular level. Studies will include the development of immunochemical methods for detection of nascent receptor polypeptides and receptor synthesis in cell free protein synthesizing systems. Combination of these techniques will provide a means for direct study of receptor synthesis at the translational and transcriptional level. Studies of ACh-receptor regulation should serve as a model for the study of other receptors. Control of receptor synthesis may be involved in the regulation of synapse formation, and thereby in the mechanism of establishment of synaptic specificity. Regulation of ACh-receptor content is perturbed in the experimental autoimmune animal model for myasthenia gravis. Studies of this experimental model may lead to improved therapeutic treatment of the human disease. They may also serve in understanding other receptor diseases.
| Smith, M M; Merlie, J P; Lawrence Jr, J C (1989) Ca2+-dependent and cAMP-dependent control of nicotinic acetylcholine receptor phosphorylation in muscle cells. J Biol Chem 264:12813-9 |
