The phenomenon of dendritic protein synthesis in neurons has been well documented. The specific mRNAs for several proteins with specific dendritic functions or localizations are thought to be targeted to sites of active translation in dendrites. This protein synthesis is associated with the postsynaptic side of synaptic contacts and may provide a mechanism for modulation of postsynaptic functional plasticity. However, the mechanisms for specific transport and targeting of RNA, to dendrites have not been delineated. This application will examine the specific structural elements responsible for localization of BC1, a short, neuron- specific RNA, to dendrites. The specific sequence elements required for targeting to dendrites will be determined and their ability to target foreign chimeric RNA sequences to the dendrite will be evaluated. In the second series of experiments, the role of electrical activity and synaptic transmission on the expression and transport of RNA into dendrites will be assessed. The effects of inhibitors for synaptic transmission, electrical activity, and cytoskeletal organization on various components of the translational apparatus will be examined. It is hoped that these studies will provide new insights into the role of dendritic protein synthesis in neuronal plasticity.
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