Faculty and Research Activities
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Margaret M Maimone, Ph.D.
Assistant Professor of Cell and Developmental Biology
147 Weiskotten Hall
Upstate Medical University
750 East Adams Street
Syracuse, NY 13210
(315) 464-8526
| Education and Clinical Training
Ph.D.: 1990, Washington University, St. Louis
Postdoctoral Fellow: Washington University, St. Louis
Research Program and Department Affiliations
Cell and Developmental Biology
Research Interests Development of the vertebrate neuromuscular junction; molecular analysis of postsynaptic proteins such as nicotinic acetylcholine receptors, rapsyn, and alpha-dystrobrevin.
Research Abstract
One of the central issues in neuroscience is the molecular mechanisms underlying the formation of chemical synapses. The vertebrate neuromuscular junction is a prototypical synapse that transmits the signal for muscle contraction from motor nerve to muscle via highly specialized pre- and postsynaptic structures. The postsynaptic membrane contains high density clusters of nicotinic acetylcholine receptor (AChR) positioned precisely opposite the branches of the presynaptic nerve terminal. These AChR clusters are critical to synapse function. The goal of our research is to determine the molecular mechanisms underlying the formation and maintenance of AChR clusters at the neuromuscular junction. Currently, we are studying two postsynaptic proteins, rapsyn and alpha-dystrobrevin, that are involved in AChR clustering. Rapsyn is required for the formation of AChR clusters and appears to interact directly with the receptor, while alpha-dystrobrevin is required for the maturation and maintenance of AChR clusters. To investigate the mechanism by which rapsyn induces AChR clustering, we are using molecular biological techniques to study the protein-protein interactions between rapsyn and the AChR during cluster formation in a cell culture system. We use site-directed mutagenesis to generate AChR mutants, express the mutants in cell lines along with rapsyn, and assess rapsyn induced AChR clustering by immunofluorescence microscopy. Our studies of alpha-dystrobrevin have been focused on examining the specific functions of the various isoforms which are generated by alternative splicing. We are using muscle cell cultures, transgenic Xenopus tadpoles, and biochemical analyses to examine each alpha dystrobrevin isoform for its subcellular location, developmental pattern of expression and ability to interact with other muscle proteins. Together these studies will help elucidate the molecular mechanisms underlying formation and maintenance of the very complex postsynaptic structure, and may also help to define the molecular basis for some forms of human congenital myasthenic syndromes or congenital muscular dystrophy.
Selected References
Enigk, R.E. and Maimone, M.M.: Differential expression and developmental regulation of a novel alpha-dystrobrevin isoform in muscle. Gene 238: 479-488, 1999.
Maimone, M.M. and Enigk, R.E.: The intracellular domain of the nicotinic acetylcholine receptor alpha subunit mediates its coclustering with rapsyn. Mol. Cell. Neurosci. 14: 340-354, 1999.
Grady, R.M., Grange, R.W., Lau, K.S., Maimone, M.M., Nichol, M.C., Stull, J.T. and Sanes, J.R.: Role for alpha-dystrobrevin in the pathogenesis of dystrophin-dependent muscular dystrophies. Nature Cell Biol. 1: 215-220, 1999.
Publications - link to PubMed
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This profile was last updated on 10/31/2006
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http://www.upstate.edu/cdb/faculty.php?ID=maimonem
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