Faculty : Departmental- Primary

Richard L. Rotundo, Ph.D.

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. 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.



Select Publications

  • 2018 Garcia, S., Nissanka, N., Mareco, E., Rossi, S.G., Peralta, S., Diaz, F., Rotundo, R.L., Carvalho, R., and Moraes, C.T. Overexpression of PGC-1α in aging muscle enhances a sub-set of young-like molecular patterns. Aging Cell 2018; 12707.https://doi.org/10.1111/acel.12707
  • 2017 Rotundo, R.L. Biogenesis, Assembly and Trafficking of Acetylcholinesterase. J. Neurochem. 142: 52-58 (2017).
  • 2015 Ruiz, C.A., Rossi, S.G., and Rotundo, R.L., Rescue and Stabilization of Acetylcholinesterase in Skeletal Muscle by N-Terminal Peptides Derived from the Non-Catalytic Subunits. J Biol Chem. 290: 20774–20781
  • 2013 Wang X, Pickrell AM, Rossi SG, Pinto M, Dillon LM, Hida A, Rotundo RL, Moraes CT.Transient systemic mtDNA damage leads to muscle wasting by reducing the satellite cell pool. Hum Mol Genet. 2013 Oct 1;22(19):3976-86. doi: 10.1093/hmg/ddt251. Epub 2013 Jun 10.
  • 2012 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 (7): 2324-2334
  • 2011 Emilio Marrero; Susana G. Rossi; Andrew Darr; Pantelis Tsoulfas; Richard L. Rotundo Translational regulation of acetylcholinesterase by the RNA-binding protein pumilio-2 at the neuromuscular synapse Journal of Biological Chemistry. 2011;286(42):36492-36499.
  • 2009 Carlos A. Ruiz; Richard L. Rotundo Dissociation of transcription, translation, and assembly of collagen-tailed acetylcholinesterase in skeletal muscle Journal of Biological Chemistry. 2009;284(32):21488-21495.
  • 2009 Carlos A. Ruiz; Richard L. Rotundo Limiting role of protein disulfide isomerase in the expression of collagen-tailed acetylcholinesterase forms in muscle Journal of Biological Chemistry. 2009;284(46):31753-31763.
  • 2009 Tina Wenz; Susana G. Rossi; Richard L. Rotundo; Bruce M. Spiegelman; Carlos T. Moraes Increased muscle PGC-1α expression protects from sarcopenia and metabolic disease during aging Proceedings of the National Academy of Sciences of the United States of America. 2009;106(48):20405-20410.
  • 2009 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).
  • 2008 R.L. Rotundo; C.A. Ruiz; E. Marrero; L.M. Kimbell; S.G. Rossi; T. Rosenberry; A. Darr; P. Tsoulfas Assembly and regulation of acetylcholinesterase at the vertebrate neuromuscular junction Chemico-Biological Interactions. 2008;175(1-3):26-29.
  • 2005 Richard L. Rotundo; Susana G. Rossi; Lewis M. Kimbell; Carlos Ruiz; Emilio Marrero Targeting acetylcholinesterase to the neuromuscular synapse Chemico-Biological Interactions. 2005;157-158:15-21.
  • 2004 Lewis M. Kimbell; Kinji Ohno; Andrew G. Engel; Richard L. Rotundo C-terminal and Heparin-binding Domains of Collagenic Tail Subunit Are Both Essential for Anchoring Acetylcholinesterase at the Synapse Journal of Biological Chemistry. 2004;279(12):10997-11005.
  • 2003 Richard L. Rotundo Expression and localization of acetylcholinesterase at the neuromuscular junction Journal of Neurocytology. 2003;32(5-8):743-766.
  • 2003 Susana G. Rossi; Ian M. Dickerson; Richard L. Rotundo Localization of the Calcitonin Gene-related Peptide Receptor Complex at the Vertebrate Neuromuscular Junction and Its Role in Regulating Acetylcholinesterase Expression Journal of Biological Chemistry. 2003;278(27):24994-25000.

View published research articles by Dr. Rotundo in the National Library of Medicine.