Associate Dean for Graduate Studies
Ph.D.: 1988, University of Southern California
Postdoctoral: Stanford University School of Medicine
The main focus of our research is directed toward understanding the cellular and molecular mechanism that control synapse formation, stabilization, elimination and remodeling. The model synapse that we study is the neuromuscular junction. In particular, we are interested in the cellular mechanisms that control the distribution of synapse specific molecules at the neuromuscular junction. One such molecule is the protein agrin. Agrin is a heparan sulfate proteoglycan. Agrin binds to synaptic basal lamina, and interacts with its receptor on the muscle fiber membrane to induce the formation of the postsynaptic apparatus. Since agrin plays a central role in the formation of the neuromuscular junction, it is likely that agrin will play a role in synapse elimination and synaptic remodeling. Experiments performed in this laboratory have revealed that agrin is quickly removed from synaptic basal lamina during normal synaptic retraction in adult frogs. During reinnervation agrin is completely removed from abandoned synaptic sites in which synaptic activity is present, while in contralateral control muscle that are inactive, agrin will remain bound to synaptic basal lamina. Decreasing synaptic activity during reinnervation delays the removal of agrin from synaptic basal lamina. These results are consistent with the hypothesis that synaptic activity controls a cellular mechanism that directs the removal of agrin from synaptic basal lamina. We hypothesize that synaptic activity causes the release or activation of proteases that cleave agrin from synaptic basal lamina.
Left to right: Marianna Rodova (Postdoctoral Fellow), Mike Werle (PI),
Ashley Burdex (Undergraduate Summer Research)