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------------------------------------------------------------------------------------------------- Curriculum Vitae B.S.,
Purdue University 1971 ------------------------------------------------------------------------------------------------- Research Interests The vertebrate neuromuscular junction (NMJ) has long been used as a model for studying the development and function of synapses. My laboratory studies the biogenesis and regulation of acetylcholinesterase (AChE), the enzyme responsible for terminating neurotransmission at cholinergic synapses, as a marker for nerve-muscle interactions. This enzyme is a prominent marker of the neuromuscular synapse because it is readily visualized with histochemical reactions, fluorescent antibodies and a specific fluorescent toxin, Fasciculin-2. The AChE molecule is composed of several subunits, catalytic and non-catalytic, and exists in a variety of oligomeric forms depending upon their subcellular location and site of cell surface attachment. The non-catalytic subunits are largely targeting molecules that insure that the enzyme is localized to the correct synaptic domain.
Several well funded ongoing research projects in our lab include the role of the non-catalytic subunits in AChE assembly. Intracellularly they can act as molecular chaperones to induce oligomerization and prevent degradation, whereas extracellularly they interact with other proteins to secure the enzyme at specialized structures on the cell surface. A second project involves studies on the muscle specific tyrosine kinase receptor MuSK and its role in regulating the clustering of AChE with other synaptic components in skeletal muscle as well as expression of the AChE and MuSK genes themselves. A third project involves the modulation of muscle AChE expression using specific peptides that can mimic portions of the non-catalytic subunits. Thus several more basic and theoretical studies converge with more applied studies resulting in a research program that extends from the cell and molecular biology of synapse formation to the regulation of AChE at the organismic level. ------------------------------------------------------------------------------------------------- Selected Publications (For a more comprehensive list go to the Laboratory of Cellular and Molecular Neurobiology Page) Rotundo, R.L., Rossi, S.G., and Peng, H.B., Targeting Acetylcholinesterase Molecules to the Neuromuscular Synapse. J. Physiol. (Paris) 92: 195-198 (1998). Peng, H.B., Xie, H., Rossi, S.G., and Rotundo, R.L., Acetylcholinesterase Clustering at the Neuromuscular Junction Involves Perlecan and Dystroglycan. J. Cell Biol. 145: 911?921 (1999). Rossi, S.G., Vazquez, A.E., and Rotundo, R.L., Local Control of Acetylcholinesterase Gene Expression in Multinucleated Skeletal Muscle Fibers. J. Neurosci. 20: 919-928 (2000). Adams, M.E., Kramarcy, N.,Krall, S.P., Rossi, S.G., Rotundo, R.L., Sealock, R., and Froehner, S.C., Absence of a-Syntrophin Leads to Structurally Aberrant Neuromuscular Synapses Deficient in Utrophin. J. Cell Biol. 150: 1385-1397, (2000). Jacobson, C., Côté, P., Rossi, S.G., Rotundo, R.L., and Carbonetto, S.. The Dystroglycan Complex is Necessary for Stabilization of Acetylcholine Receptor Clusters at Neuromuscular Junctions and Formation of the Synaptic Basal Lamina. J. Cell Biol. 152: 435-450 (2001). Drapeau, P., Buss, R.R., Ali, D.W., Legendre, P., and Rotundo, R.L. Synaptic Organization Limits the Development of Fast Neuromuscular Transmission. J. Neurophysiol. 86: 2951-2956 (2001). Arikawa-Hirasawa, E., Rossi, S.G., Rotundo, R.L., and Yamada, Y., Absence of Acetylcholinesterase at the Neuromuscular Junctions of Perlecan-null Mice. Nature Neuroscience 5:119-123 (2002). Rossi SR, Dickerson I, Rotundo RL. (2003) Localization of the CGRP receptor complex at the vertebrate neuromuscular junction and its role in regulating acetylcholinesterase biogenesis. J Biol Chem 278: 24994-25000. Rotundo, RL (2003) Expression and localization of acetylcholinesterase at the neuromuscular junction. J Neurocytology 32: 743-766. Kimbell KM, Ohno K, Engel AG, Rotundo RL. (2004) C-Terminal and heparin-binding domains of collagenic tail subunit are both essential for anchoring acetylcholinesterase at the synapse. J Biol Chem 279:10977-11005. Rotundo RL, Rossi SG, Kimbell LM, Ruiz C, Marerro E. (2005) Targeting Acetylcholinesterase to the Neuromuscular Synapse. Chemico-Biological Interactions 157-158:15-21.
View published research articles by Dr. Rotundo in the National Library of Medicine
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