Naim, Nyla
(2018)
LUMINESCENCE-ACTIVATED CYCLASE ALLOWS LOCALIZED PHOTO AND CHEMICAL STIMULATION OF cAMP SYNTHESIS.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger that regulates cellular proliferation, differentiation, attachment, migration, and several other processes. It has become increasingly evident that tight regulation of cAMP accumulation and localization confers divergent yet specific signaling to pathways downstream. Currently, few tools are available with sufficient spatial and temporal resolution to study location-biased cAMP signaling. Here, we introduce a new fusion protein consisting of a light-activated cyclase (bPAC) and luciferase (nLuc). This novel construct allows dual activation of cAMP production using temporally precise photostimulation or chronic chemical stimulation. Furthermore, we directed this construct to various subcellular compartments to improve spatial resolution. Using a combination of FRET imaging and optogenetics, we investigate location-biased signaling in thyroid epithelial mitogenesis and potential applications of bPAC-nLuc in vivo. A better understanding of the physical interactions and dynamics between cAMP and multiple signaling pathways may provide new therapeutic approaches for treating diseases with aberrant cAMP signaling.
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| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
25 September 2018 |
| Date Type: |
Publication |
| Defense Date: |
30 July 2018 |
| Approval Date: |
25 September 2018 |
| Submission Date: |
6 September 2018 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
132 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Molecular Pharmacology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
cyclic AMP, cell signaling, compartmentalization, optogenetics, luminescence |
| Date Deposited: |
25 Sep 2018 12:49 |
| Last Modified: |
25 Sep 2019 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/35305 |
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