Bruce G. Wallace, Ph.D. Professor Department of Physiology & Biophysics Assistant Dean Essentials Core Curriculum
	UCHSC at Fitzsimons RC-1 North Tower, P18-7113 PO Box 6511, Mail Stop F8307 Tel (303) 724-2068 Fax (303) 724-4501	E-mail: bruce.wallace@UCHSC.edu Curriculum vitae BNAT program member

RESEARCH

MECHANISM OF SYNAPSE FORMATION

·  At synapses throughout the nervous system there are structural specializations that play a crucial role in synaptic transmission. For example, axon terminals have active zones which are involved in the release of transmitter and target cells have a postsynaptic apparatus that includes aggregates of receptors for the transmitter. Studies of the vertebrate skeletal neuromuscular junction have shown that the formation and maintenance of synaptic specializations relies on an exchange of signals between the axon terminal and the muscle fiber. To understand how synapses form it is necessary to identify these signals, ascertain how their expression is regulated, and determine the mechanisms by which they induce synaptic differentiation.
·  Our laboratory is investigating the mechanism of action of one such signal, agrin, which is released by axon terminals to induce the formation of postsynaptic specializations on muscle fibers. In our experiments we study the effects of agrin on myofibers grown in cell culture. Using histochemical and immunohistochemical techniques we have found that agrin induces specializations on cultured myofibers at which several components of the postsynaptic apparatus are aggregated, including acetylcholine receptors and acetylcholinesterase. Several lines of evidence are consistent with the hypothesis that the formation of aggregates of acetylcholine receptors is mediated by agrin-induced increases in protein tyrosine phosphorylation, including phosphorylation of one of the acetylcholine receptor subunits.
·  Current studies focus on the role of tyrosine phosphorylation in the regulation of acetylcholine receptor distribution, identification and characterization of the protein tyrosine kinases activated by agrin, and the mechanism of aggregation of other components of the postsynaptic apparatus.

Selected Publications

Wallace, B.G. 1994. Staurosporine inhibits agrin-induced acetylcholine receptor phosphorylation and aggregation. J. Cell Biol. 125:661-668. pdf

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. pdf

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. pdf

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 alpha-dystroglycan. EMBO J., 15:2625-2631. pdf

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. pdf

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. pdf

Meier, T. and Wallace, B.G. 1998. Formation of the neuromuscular junction: molecules and mechanisms. BioEssays 20:819-829. pdf

PubMed search (Wallace B)