The nicotinic acetylcholine receptor (AChR) of mammalian muscle is a multimeric integral membrane glycoprotein functioning as a neurotransmitter receptor and a transmembrane ion channel. It is clear that the AChR plays a key role in neuromuscular transmission and it has been extensively studied at the biochemical and electrophysiological level. Additional studies are needed, however, to elucidate the molecular mechanisms involved in the assembly, insertion and regulation of important membrane proteins such as the AChR. Monoclonal antibodies provide the needed specificity and affinity to be extremely useful tools in such studies. Information concerning the regulation of the levels of synthesis of the AChR could be of considerable importance for myasthenia gravis where a deficit of functional AChR is clearly the basis for the clinical manifestations of the disease. The proposed research involves the use of monoclonal antibodies against mammalian AChR to study the in vivo biosynthesis and regulation of the receptor complex and its individual subunits. In this work I plan to use established mouse muscle cell lines which produce AChR. Furthermore, the techniques of somatic cell genetics will be applied in order to obtain mutant variants with altered structure or with defective biosynthesis of the AChR. Such variants would expand our knowledge of the biogenesis of cell surface receptors and other functional membrane proteins and would facilitate and complement studies of the genetic regulation of these membrane proteins.
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