Professor
Department of Physiology and Biophysics
UCD at Fitzsimons

RC-1 North Tower, P18-7125. PO Box 6511, Mail Stop F8307. Tel (303) 724-4532. Fax (303) 724-4501.
Email Bruce.Wallace@UCHSC.edu

| Education | Academic Appointments | Research Program | Selected Publications |

• 1969 B.A. Amherst College, Amherst, Massachusetts
  
• 1974 Ph.D. Department of Neurobiology, Harvard Medical School
  

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• 1975-77 NIH Postdoctoral Fellow, Stanford University School of Medicine
  
• 1977-84 Assistant Professor, Department of Neurobiology, Stanford University School of Medicine
  
• 1985-90 Senior Research Associate, Department of Neurobiology, Stanford University School of Medicine
  
• 1990-1996 Associate Professor, Department of Physiology, University of Colorado School of Medicine
  
• 1996- Professor, Department of Physiology and Biophysics, University of Colorado School of Medicine

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Our research is aimed at understanding the molecular mechanisms mediating synapse formation. Previous studies have shown that the formation of postsynaptic specializations at developing and regenerating vertebrate skeletal neuromuscular junctions is induced by agrin, a protein released from the terminals of motor axons. To investigate the mechanisms by which agrin induces postsynaptic differentiation, we are studying the effects of agrin in primary cell cultures of chick and mouse myotubes. The studies employ fluorescence microscopy coupled with computerized image analysis to measure changes in the distribution of proteins on the surfaces of cells, and affinity chromatography, protein chemistry, and molecular biological techniques to assay posttranslational modifications of specific proteins and assess their role in postsynaptic differentiation. Addition of agrin to cultured myotubes induces the formation of specializations that resemble the postsynaptic apparatus at the neuromuscular junction. Within the specializations several components accumulate in high concentration, including acetylcholine receptors and acetylcholinesterase. Several lines of evidence suggest that agrin interacts with specific receptors on the surface of the myotube to cause a localized activation of protein tyrosine kinases, resulting in increased tyrosine phosphorylation of the beta subunit of nearby acetylcholine receptors. The increase in tyrosine phosphorylation causes acetylcholine receptors, which are normally free to diffuse laterally in the plane of the membrane, to bind to the underlying cytoskeleton. Therefore, immobilized acetylcholine receptors accumulate in the vicinity of the activated agrin receptor, forming an aggregate. In addition to pursuing the role of protein tyrosine phosphorylation in the regulation of acetylcholine receptor distribution, future studies will focus on the role of protein phosphorylation in the aggregation of other components of the postsynaptic apparatus, as well as on mechanisms of presynaptic differentiation.

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• Wallace, B.G., Nitkin, R.M. Reist, N.E., Fallon, J.R., Moayeri, N.N. and McMahan, U.J. 1985. Aggregates of acetylcholinesterase induced by acetylcholine receptor-aggregating factor. Nature 315:574-577.
  
• Wallace, B.G. 1986. Aggregating factor from Torpedo electric organ induces formation of patches containing acetylcholine receptors, acetylcholinesterase, and butyrylcholinesterase on cultured myotubes. J. Cell Biol. 102:783-794.
  
• Nitkin, R.M., Smith, M.A., Magill, C., Fallon, J.R., Yao, Y-M.M., Wallace, B.G., and McMahan, U.J. 1987. Identification of agrin, a synaptic organizing protein from Torpedo electric organ. J. Cell Biol. 105:2471-2478.
  
• Wallace, B.G. 1988. Regulation of agrin-induced acetylcholine receptor aggregation by Ca++ and phorbol ester. J. Cell Biol. 107:267-278.
  
• Wallace, B.G. 1989. Agrin-induced specializations contain cytoplasmic, membrane, and extracellular matrix-associated components of the postsynaptic apparatus. J. Neurosci. 9:1294-1302.
  
• McMahan, U.J., and Wallace, B.G. 1989. Molecules in basal lamina that direct formation of synaptic specializations at neuromuscular junctions. Dev. Neurosci. 11:227-247.
  
• Wallace, B.G. 1990. Inhibition of agrin-induced acetylcholine receptor aggregation by heparin, heparan sulfate, and other polyanions. J. Neurosci. 10:3576-3582.
  
• Wallace, B.G. 1991. The mechanism of agrin-induced acetylcholine receptor aggregation. Phil. Trans. Roy. Soc. B. 331:273-280.
  
• Wallace, B.G., Qu, Z., and Huganir, R.L. 1991. Agrin induces phosphorylation of the nicotinic acetylcholine receptor. Neuron 6:869-878.
  
• Nicholls, J.G., Martin, A.R., and Wallace, B.G. 1992. From Neuron to Brain, 3rd ed., Sinauer Associates, Sunderland, MA.
  
• Wallace, B.G. 1992. Mechanism of agrin-induced acetylcholine receptor aggregation. J. Neurobiol. 23:592-604.
  
• Wallace, B.G. 1994. Staurosporine inhibits agrin-induced acetylcholine receptor phosphorylation and aggregation. J. Cell Biol. 125:661-668.
  
• Wallace, B.G. 1995. Regulation of the interaction of nicotinic acetylcholine receptors with the cytoskeleton by agrin-activated protein tyrosine kinase. J. Cell Biol. 128:1121-1129.
  
• Meier, T., Perez, G.M., and Wallace, B.G. 1995. Immobilization of nicotinic acetylcholine receptors in mouse C2 myotubes by agrin-induced protein tyrosine phosphorylation. J. Cell Biol. 131, 441-451.
  
• Meier, T., Gesemann, M., Cavalli, V., Ruegg, M.A., and Wallace, B.G.. 1996. AChR phosphorylation and aggregation induced by an agrin fragment that lacks the binding domain for a-dystroglycan, EMBO J. 15:2625-2631.
  
• Meier, T., Ruegg, M.A., and Wallace, B.G. 1998. Muscle-specific agrin isoforms reduce phosphorylation of AChR gamma and delta subunits in cultured muscle cells. Mol. Cell Neurosci. 11:206-216.
  
• Meyer, G. and Wallace, B.G. 1998. Recruitment of a nicotinic acetylcholine receptor mutant lacking cytoplasmic tyrosine residues in its beta subunit into agrin-induced aggregates. Mol. Cell. Neurosci. 11:324-333.
  
• Meier, T. and Wallace, B.G. 1998. Formation of the neuromuscular junction: molecules and mechanisms. BioEssays 20:819-829.

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