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.

 

 

(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.  

 

Rotundo R L (2009) Neuromuscular Junction (NMJ): Acetylcholinesterases. In: Squire LR (ed.) Encyclopedia of Neuroscience, volume 6, pp. 551-558. Oxford: Academic Press.

 

Ruiz , C.A.and Rotundo, R.L., Dissociation of Transcription, Translation and Assembly of Collagen Tailed Acetylcholinesterase in Skeletal Muscle.  J. Biol. Chem., 284: 21488-21495 (2009).

 

Ruiz , C.A.and Rotundo, R.L.,  Limiting Role of Protein Disulfide Isomerase in the Expression of Collagen-tailed Acetylcholinesterase in Muscle.  J. Biol. Chem., published online Sept 16, 2009.