Richard L. Rotundo, Ph.D.
Professor of Cell Biology, Physiology and Biophysics, Biochemistry and Molecular Biology, and Member of Neurosciences Program
Rosenstiel Medical Science Building - 4168
B.S., Purdue University 1971
M.S., University of Connecticut 1975
Ph.D., University of Connecticut 1976
Postdoctoral Fellow, Carnegie Institution of Washington, 1976-1980
Associate Staff Member, Carnegie Institution of Washington,
Dept. of Embryology 1980-1984
Assistant Professor, University of Miami 1984-1989
Associate Professor, University of Miami 1989-1993
Professor, University of Miami 1993-present
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 on subcellular location and site of attachment. The non-catalytic subunits are largely targeting molecules that insure enzyme is localized to the correct synaptic domain.
Several funded ongoing research projects in our lab include the role of the non-catalytic subunits in AChE assembly, protein folding, regulation by RNA binding proteins, and alternative functions of AChE. Intracellulary, the non-catalytic subunits can act as molecular chaperones to induce oligomerization and prevent degradation, whereas extracellulary they interact with other proteins to secure the enzyme at specialized structures on the cell surface. A second project involves the translational regulation of AChE by the RNA binding protein Pumilio2 that is highly localized to the NMJ. A third project involves the modulation of muscle AChE expression using specific peptides that can mimic portions of the non-catalytic subnits. Finally, we are also studying the function of AChE, in the sea anemone, Nematostella, whose genome has been sequenced, as a model for the evolutionary origin of synapses. Thus several 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.
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(For a more comprehensive list go to the Laboratory of Cellular and Molecular Neurobiology Page)
Wang, X., Pickrell, A.M., Rossi, S.G., Pinto, M., Dillon, L.M., Hida, A., Rotundo, R.L.,
and Moraes, C.T., Transient systemic mtDNA damage leads to muscle wasting by reducing the satellite cells pool. Hum Mol Genet 22:3976-3986 (2013).
Amenta, A.R., Creely, H.E., Mercado, M.L.T., Hagiwara, H., McKechnie, B.A., Lechner, B.E., Rossi, S.G., Wang, Q., Owens, R.T., Marrero, E., Mei, L., Hoch, W., Young, M.F., McQuillan, D.J., Rotundo, R.L.
and Fallon, J.R., Biglycan Is an Extracellular MuSK Binding Protein Important for Synapse Stability, J. Neurosci. 32: 2324-2334 (2012).
Wenz, T., Rossi, S.G., Rotundo, R.L.,
Spiegelman, B., and Moraes, C., Increased muscle PGC-1α expression protects from sarcopenia and metabolic disease during aging. Proc. Natl. Acad. Sci. , 106: 20405-20410 (2009).
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, S.R., Dickerson, I., Rotundo, R.L
. (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
Kimbell, K.M., Ohno, K., Engel, A.G., Rotundo, R.L
. (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, R.L., Ruiz, C.A., Marrero, E., Rossi, S.G., Rosenberry, T., Darr, A., and Tsoulfas, P., Assembly and Regulation of Acetylcholinesterase at the Vertebrate Neuromuscular Junction. Chemico-Biological Interactions 175:26-29 (2008).
Rotundo, R.L. (2009) Neuromuscular Junction (NMJ): Acetylcholinesterases. In: Squire LR (ed.) Encyclopedia of Neuroscience, volume 6, pp. 551-558. Oxford: Academic Press.
Marrero, E., Rossi, S.G., Darr, A., Tsoulfas, P, Rotundo, R.L.
Translational regulatino of acetylcholinesterase by the RNA-binding protein pumilio-2 at the neuromuscular synapse. J. Biol. Chem., 2011 Aug 24 [Epub ahead of print] PMID:21865157
View published research articles by Dr. Rotundo in the National Library of Medicine