This research project focuses on understanding how the machinery to generate proteins is assembled in polarized cells. Polarity is critical for function of eukaryotic cells, particularly for the neurons studied here that use polarized domains to transmit all signals for movement and sensation within the brain and spinal cord. Cellular polarity is determined in part by trafficking of messenger RNAs (mRNA) and translational machinery for spatially localizing protein synthesis in subcellular compartments. A surprising finding from recent studies in neurons is that mRNAs encoding components of the ribosome, the macromolecular complex that synthesizes proteins, are transported into distal processes of neurons. All previous work had indicated that ribosomes are assembled in the cell's nucleus and then transported as intact subunits to other compartments of the cell. The discovery of mRNAs encoding ribosome components in neuronal processes suggests that some assembly of ribosomes may occur locally at the periphery of these cells. This project aims to determine the functional role that ribosomal protein (RP) mRNA localization serves in the neuron. The aims will determine if localized RP mRNAs are used to synthesize proteins, if locally synthesized RPs are added to the ribosome in neuronal processes, and if ribosome function is altered locally by addition of RPs. The outcome of these studies will increase understanding of how polarized cells can manipulate their makeup of proteins locally and whether ribosome structure or function can be locally altered under different environmental conditions.
The broader impacts of this proposal are two-fold. First, though the work here is limited to neurons, the implications for localized synthesis of ribosome components is broadly applicable to other cell types. Cells smaller than neurons also have polarity that is determined in part by spatial control of protein synthesis. However, small cell types are not as amenable to the molecular and biochemical analyses that can be performed with the cultured neurons that will be used here. The knowledge and scientific approaches developed here can be readily applied to other model systems. Second, this project will work with Teaching Faculty in the Biology Department to actively engage undergraduate students in the research objectives through the co-operative educational opportunities at Drexel University. This will bring new opportunities for students in an intensive basic research environment, providing them with significant additional training and educational experiences within the lab that will bolster their chances for future employment in a science field and their opportunities for graduate work in Biology.
