The Role Of eIF4E In Nociception Of Drosophila Melanogaster
- ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
- Katherine Machen (Creator)
- Institution
- Appalachian State University (ASU )
- Web Site: https://library.appstate.edu/
- Advisor
- Andrew Bellemer
Abstract: Some cases of chronic pain arise from inappropriate sensitization as a result of changes in gene expression within the sensory neuron. Translational regulation is a known contributor to the required changes in gene expression. A known node for translational regulation is the mRNA cap-binding protein, eIF4E. In this study, we hypothesize that eIF4E is also the mechanism used by the pronociceptive hedgehog (Hh) signaling pathway. Utilizing Drosophila melanogaster, the overexpression of the dominant-negative version of Patched (ptcDN) protein, a manipulation known to activate the hedgehog signaling pathway, was confirmed to induce sensitization of sensory neurons. Separately, the knockdown of eIF4E-4 and eIF4E-1 resulted in a partial loss of thermal nociception. In line with previous work, the nociceptor-specific knockdown of eIF4E-1 did prevent the onset of sensitization following tissue damage. The knockdown of eIF4E-1 and the overexpression of ptcDN in the nociceptors resulted in an attenuation of the expected sensitization. These results point to eIF4E-1 being an effector of the canonical Hh signaling pathway. Specifically, the Hh signaling pathway utilizes the eIF4F complex to regulate translation over pronociceptive mRNA. This determination provides further insight into the Hh signaling pathway and eIF4E as potential therapeutic targets for chronic pain.
The Role Of eIF4E In Nociception Of Drosophila Melanogaster
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Created on 8/2/2022
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Additional Information
- Publication
- Thesis
- Machen, K. (2021). The Role Of eIF4E In Nociception Of Drosophila Melanogaster. Unpublished Master’s Thesis. Appalachian State University, Boone, NC.
- Language: English
- Date: 2021
- Keywords
- Drosophila, Nociception, Nociceptor sensitization, eIF4E, translational regulation