Molecular Substrates of Translation at the Synapse

Scripps Florida, Jupiter FL

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Abstract

DESCRIPTION (provided by applicant): Despite decades of research on the significance of local translation in memory storage, very little is known about the identity of the different RNAs translated at specific synapses, the temporal window of their stoichiometric changes, and how they are utilized at synapses in any system. RNAs are actively transported to synapses as ribo-nucleoprotein complexes by molecular motors. There are more than 40 different RNA binding proteins identified in a mouse brain. We have developed a genomics approach to identify all RNAs transported to synapses by focusing on the actively transported ribo-nucleoprotein complexes. This strategy involves isolation and characterization of immunoprecipitated molecular motor complexes from the tissue of interest. We propose to identify and characterize coding and noncoding RNAs transported to the hippocampal and prefrontal cortex (PFC) synapses by isolation and characterization of protein complexes transported by kinesin, a microtubule dependent molecular motor that moves from the cell-body to distal neuronal processes. The long-term goal of this project is to identify and characterize molecular substrates of synaptic translation and their temporal regulation during initiation and persistence of long-term memory storage at the hippocampal and PFC synapses, the two critical brain regions involved in storage and consolidation of long-term memories. PUBLIC HEALTH RELEVANCE: Focusing on the hippocampal and prefrontal cortex neurons of the mouse brain, this project will identify all the coding and noncoding RNAs that are actively transported to synapses. This data will be used to identify and characterize signaling networks at the synapse that are regulated by local translation during storage and consolidation of long-term memories.