Shining light on TrkA : an optobiological approach to dissecting location-specific TrkA signaling
Abstract/Contents
- Abstract
- Nerve growth factor (NGF) and its primary receptor, tropomyosin receptor kinase A (TrkA), play a crucial role in neuronal development, differentiation, and survival. Aberrant TrkA signaling has been implicated in chronic neuropathic and nociceptive pain disorders, neurodegenerative disorders, and cancers. It has been hypothesized that after endocytosis of the active receptor, TrkA continues to signal from the endosome. Although neurotrophin biology has been an active field of study for almost 70 years, questions around the identity of the signaling endosome and the impact of the location and duration of receptor activation have remained unanswered, due to the limitations of traditional cell biology methods. In this work, we have leveraged the light-induced protein-protein interaction system iLID to construct opto-TrkA, a version of this receptor that is activated by blue light rather than its endogenous ligand. This system permits rapid, reversible, location-specific activation of TrkA in cellular systems as well as model organisms. We have demonstrated that opto-TrkA is capable of reproducing key hallmarks of endogenous TrkA signaling in a cellular model. We offer the system for use in dissecting the contributions of TrkA at different subcellular compartments to the overall cell response. Further, we have begun to demonstrate the utility of opto-TrkA in model organisms. It is our hope that this system will be an invaluable tool in expanding our understanding of neurotrophin biology.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Hope, Jen Marrero |
|---|---|
| Degree supervisor | Cui, Bianxiao |
| Thesis advisor | Cui, Bianxiao |
| Thesis advisor | Cegelski, Lynette |
| Thesis advisor | Lin, Michael |
| Degree committee member | Cegelski, Lynette |
| Degree committee member | Lin, Michael |
| Associated with | Stanford University, Department of Chemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Jen Marrero Hope. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/vg155xz1071 |
Access conditions
- Copyright
- © 2021 by Jen Marrero Hope
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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