Neuronal plasticity arises from the regulation of gene expression by plasma membrane excitation. In cells undergoing """"""""plastic"""""""" changes a signaling pathway must exist which couples the membrane to macromolecular synthesis. We plan to study this pathway (or pathways), whose molecular details are not known, in the vertebrate skeletal muscle fiber, a simple model system that displays activity-controlled modulation of protein composition. Because of the magnitude and speed of the response, the acetylcholine receptor synthesis rate is selected as an indicator of """"""""plastic"""""""" change. We will attempt to establish the level (transcriptional vs. post-transcriptional) at which receptor synthesis is regulated by measuring concentrations of receptor mRNA and correlating them with observed rates of receptor subunit synthesis, assembly and appearance in the plasma membrane. These studies will be carried out with adult chicken muscle under conditions of denervation and reinnervation (which lead to dramatic increases and decreases, respectively, of receptor synthesis rate), and with cultured chick embryo myotubes, which modulate their acetylcholine receptor output in response to various chemical and pharmacological stimuli. Initially, the investigation will be restricted to the -subunit of the receptor because all required molecular tools are already available for this peptide chain. Subsequently, similar analyses will be carried out on the remaining polypeptide components. Eventually we hope to identify the second messenger involved in control of receptor synthesis and to provide a complete description of how muscle membrane activity and receptor expression are coupled.

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National Institute of Neurological Disorders and Stroke (NINDS)
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Neurological Sciences Subcommittee 1 (NLS)
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State University New York Stony Brook
Schools of Medicine
Stony Brook
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Spinner, Daryl S; Liu, Shaohua; Wang, Shao-Wen et al. (2002) Interaction of the myogenic determination factor myogenin with E12 and a DNA target: mechanism and kinetics. J Mol Biol 317:431-45
Liu, S; Spinner, D S; Schmidt, M M et al. (2000) Interaction of MyoD family proteins with enhancers of acetylcholine receptor subunit genes in vivo. J Biol Chem 275:41364-8
Neville, C M; Choe, Y H; Lee, Y S et al. (1998) The E protein CTF4 and acetylcholine receptor expression in development and denervation supersensitivity. J Biol Chem 273:14046-52
Malik, S; Huang, C F; Schmidt, J (1995) The role of the CANNTG promoter element (E box) and the myocyte-enhancer-binding-factor-2 (MEF-2) site in the transcriptional regulation of the chick myogenin gene. Eur J Biochem 230:88-96
Huang, C F; Flucher, B E; Schmidt, M M et al. (1994) Depolarization-transcription signals in skeletal muscle use calcium flux through L channels, but bypass the sarcoplasmic reticulum. Neuron 13:167-77
Huang, C F; Lee, Y S; Schmidt, M M et al. (1994) Rapid inhibition of myogenin-driven acetylcholine receptor subunit gene transcription. EMBO J 13:634-40
Huang, C F; Neville, C M; Schmidt, J (1993) Control of myogenic factor genes by the membrane depolarization/protein kinase C cascade in chick skeletal muscle. FEBS Lett 319:21-5
Jia, H T; Tsay, H J; Schmidt, J (1992) Analysis of binding and activating functions of the chick muscle acetylcholine receptor gamma-subunit upstream sequence. Cell Mol Neurobiol 12:241-58
Neville, C M; Schmidt, J (1992) Expression of myogenic factors in skeletal muscle and electric organ of Torpedo californica. FEBS Lett 305:23-6
Neville, C M; Schmidt, M; Schmidt, J (1992) Response of myogenic determination factors to cessation and resumption of electrical activity in skeletal muscle: a possible role for myogenin in denervation supersensitivity. Cell Mol Neurobiol 12:511-27

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