At the neuromuscular junction, the transmission of signal from the nerve to the muscle which causes muscle contraction is mediated by the release of acetylcholine from the nerve terminal and the sensing of this molecule by the receptors in the muscle. To gain insight into the formation of the neuro-muscular junction, this study will use physiological and structural techniques to observe the development of the acetylcholine receptors in the muscle cell and the development of the acetylcholine release mechanism in the nerve terminal in tissue culture and the interaction between the nerve and the muscle during innervation. We are particularly interested in the information that the nerve cell conveys to the muscle in effecting the accumulation of acetylcholine receptors in the postjunctional membrane and the mechanism that the muscle cell uses in generating such a receptor accumulation. On the presynaptic side, we are interested in the differentiation of the nerve terminal induced by its target and the mechanism of the formation of presynaptic vesicle clusters. Besides conventional nerve-muscle cocultures, we will also study the formation of the acetylcholine receptor clusters and synaptic vesicle clusters induced by basic polypeptide-coated latex beads. Previous studies from this laboratory have shown that these compounds can induce a local pre- and postsynaptic-type differentiation. These studies are aimed at providing a fundamental understanding of the development of the muscle during innervation. This knowledge is essential for the elucidation of the cause of many neuromuscular disorders.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
Zip Code
Zhao, Xiaotao T; Qian, Yueping K; Chan, Ariel W S et al. (2007) Regulation of ACh receptor clustering by the tyrosine phosphatase Shp2. Dev Neurobiol 67:1789-801
Madhavan, Raghavan; Zhao, Xiaotao T; Reynolds, Albert B et al. (2006) Involvement of p120 catenin in myopodial assembly and nerve-muscle synapse formation. J Neurobiol 66:1511-27
Madhavan, Raghavan; Zhao, Xiaotao T; Ruegg, Markus A et al. (2005) Tyrosine phosphatase regulation of MuSK-dependent acetylcholine receptor clustering. Mol Cell Neurosci 28:403-16
Madhavan, Raghavan; Peng, H Benjamin (2005) Molecular regulation of postsynaptic differentiation at the neuromuscular junction. IUBMB Life 57:719-30
Peng, H Benjamin; Yang, Jie-Fei; Dai, Zhengshan et al. (2003) Differential effects of neurotrophins and schwann cell-derived signals on neuronal survival/growth and synaptogenesis. J Neurosci 23:5050-60
Madhavan, Raghavan; Peng, H Benjamin (2003) A synaptic balancing act: local and global signaling in the clustering of ACh receptors at vertebrate neuromuscular junctions. J Neurocytol 32:685-96
Madhavan, Raghavan; Zhao, Xiaotao T; Chan, Frances et al. (2003) The involvement of calcineurin in acetylcholine receptor redistribution in muscle. Mol Cell Neurosci 23:587-99
Dai, Z; Luo, X; Xie, H et al. (2000) The actin-driven movement and formation of acetylcholine receptor clusters. J Cell Biol 150:1321-34
Peng, H B; Xie, H; Rossi, S G et al. (1999) Acetylcholinesterase clustering at the neuromuscular junction involves perlecan and dystroglycan. J Cell Biol 145:911-21
Fu, A K; Smith, F D; Zhou, H et al. (1999) Xenopus muscle-specific kinase: molecular cloning and prominent expression in neural tissues during early embryonic development. Eur J Neurosci 11:373-82

Showing the most recent 10 out of 40 publications