The Silvio Conte Center for Neuroscience Research at UCSF will explore the central hypothesis that receptors and ion channels serve as organizing centers and membrane attachment points for large, multi-protein complexes that control neuronal excitability. The Center will explore how the various proteins are trafficked and targeted to specific sites on the surface of the cell and the functional consequences of these multi-protein complexes. We have assembled a group of investigators who have common interests and goals, but who bring unique neuropharmacological approaches to the analysis of a common biological problem. We will 1) employ organisms amenable to genetics for the identification of novel genes important for receptor and ion channels aggregation, 2) use cellular, molecular and pharmacological approaches to understand the mechanisms involved in the delivery of these membrane proteins to the surface and their targeting to specific sites on the cell?s surface, and 3) use structural analysis to elucidate how the various proteins within the multi-protein complex interact with each other. Results from these studies will be of fundamental importance for understanding normal and abnormal brain function. For instance, most psychiatric and neurological diseases are believed to result from alterations in synaptic transmission and neuronal excitability. Furthermore, accumulating evidence indicates that synaptic plasticity involves the rapid and long lasting modification of the receptor composition of the postsynaptic membrane. Thus, an understanding of the principles involved in the formation and maintenance of multi-protein signaling complexes will be invaluable in the development of therapeutic drugs for conditions such as depression, schizophrenia, Alzheimer's disease and Parkinson's disease.
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