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LUMINESCENCE-ACTIVATED CYCLASE ALLOWS LOCALIZED PHOTO AND CHEMICAL STIMULATION OF cAMP SYNTHESIS

Naim, Nyla (2018) LUMINESCENCE-ACTIVATED CYCLASE ALLOWS LOCALIZED PHOTO AND CHEMICAL STIMULATION OF cAMP SYNTHESIS. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Naim, Nylanyn1@pitt.edunyn1
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBisello, Alessandroalb138@pitt.edualb138
Thesis AdvisorAltschuler, Danielaltschul@pitt.edualtschul
Committee MemberLancaster, Jackdoctorno@pitt.edudoctorno
Committee MemberRomero, Guillermoggr@pitt.eduggr
Committee MemberVilardaga, Jean-Pierrejpv@pitt.edujpv
Committee MemberKwiatkowski, Adamadamkwi@pitt.eduadamkwi
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 2018 12:49
URI: http://d-scholarship.pitt.edu/id/eprint/35305

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