The objective of the proposed research is to understand the cellular and molecular mechanism which regulate the functional expression of glutamate receptors. Glutamate receptors play critical roles in neuronal development and plasticity and in neurodegenerative disease processes. This research will identify mechanisms which mediate the regulation of glutamate receptor expression at the level of mRNA translation. The requirement during synaptic plasticity for the specific modification of individual synapses and the demonstration of dendritic synthesis of synapse-specific soluble proteins has led to the idea that local translation may be important for maintenance of changes in synaptic strength. Photobleach recovery experiments using fluorescently labeled membrane-spanning proteins, including glutamate receptor subunits, will be used to investigate the local translation of integral membrane proteins. Fluorescent reporter constructs will allow for investigation of the regulation of glutamate receptor translation by the 5? untranslated regions (5?UTRs) of receptor subunit mRNAs. This research should provide insight into mechanisms by which protein synthesis is regulated in neurons. The demonstration of dendritic glutamate receptor synthesis will enhance understanding of the processes underlying synaptic development and plasticity. The characterization of 5?UTR-mediated controlof translation will be broadly applicable to regulation of protein synthesis in various systems.
| Grigston, Jeffrey C; VanDongen, Hendrika M A; McNamara 3rd, James O et al. (2005) Translation of an integral membrane protein in distal dendrites of hippocampal neurons. Eur J Neurosci 21:1457-68 |
