This project is to explore a specific aspect of the control of acetylcholine receptor (AChR) expression by the motor nerve. The AChR, a skeletal muscle membrane protein, normally resides within the neuromuscular junction, but upon motor nerve section appears in large numbers in extrajunctional areas. Cessation of muscle activity following denervation results in the appearance of protein factors that recognize specific regulatory sequences in receptor subunit genes and upon binding activate or derepress them. Short control sequences have been identified in the AChR a- and d- subunit genes; since these elements are structurally similar, they are likely to be recognized by the same regulatory protein(s). In this project, radioactively labeled target DNA fragments will be used as ligands to identify binding proteins, and resin-coupled target DNA will be employed as an affinity chromatography matrix for the purification of such proteins. Findings made in the course of this research will aid in understanding AChR control and may shed light on how electrical activity regulates gene expression in excitable cells in general.
