The genetically encoded tool set for investigating cAMP: more than the sum of its parts

Intracellular fluctuations of the second messenger cyclic AMP (cAMP) are regulated with spatial and temporal precision. This regulation is supported by the sophisticated arrangement of cyclases, phosphodiesterases, anchoring proteins and receptors for cAMP. Discovery of these nuances to cAMP signali...

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Main Authors: Neha ePatel, Matthew G Gold
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-08-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00164/full
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author Neha ePatel
Matthew G Gold
author_facet Neha ePatel
Matthew G Gold
author_sort Neha ePatel
collection DOAJ
description Intracellular fluctuations of the second messenger cyclic AMP (cAMP) are regulated with spatial and temporal precision. This regulation is supported by the sophisticated arrangement of cyclases, phosphodiesterases, anchoring proteins and receptors for cAMP. Discovery of these nuances to cAMP signaling has been facilitated by the development of genetically encodable tools for monitoring and manipulating cAMP and the proteins that support cAMP signaling. In this review, we discuss the state-of-the-art in development of different genetically encoded tools for sensing cAMP and the activity of its primary intracellular receptor protein kinase A (PKA). We introduce sequences for encoding adenylyl cyclases that enable cAMP levels to be artificially elevated within cells. We chart the evolution of sequences for selectively modifying protein-protein interactions that support cAMP signaling, and for driving cAMP sensors and manipulators to different subcellular locations. Importantly, these different genetically encoded tools can be applied synergistically, and we highlight notable instances that take advantage of this property. Finally, we consider prospects for extending the utility of the toolset to support further insights into the role of cAMP in health and disease.
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spelling doaj.art-7b9dcb9622dc41f9b28ac5826de52cc12022-12-21T18:28:14ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122015-08-01610.3389/fphar.2015.00164152616The genetically encoded tool set for investigating cAMP: more than the sum of its partsNeha ePatel0Matthew G Gold1UCLUCLIntracellular fluctuations of the second messenger cyclic AMP (cAMP) are regulated with spatial and temporal precision. This regulation is supported by the sophisticated arrangement of cyclases, phosphodiesterases, anchoring proteins and receptors for cAMP. Discovery of these nuances to cAMP signaling has been facilitated by the development of genetically encodable tools for monitoring and manipulating cAMP and the proteins that support cAMP signaling. In this review, we discuss the state-of-the-art in development of different genetically encoded tools for sensing cAMP and the activity of its primary intracellular receptor protein kinase A (PKA). We introduce sequences for encoding adenylyl cyclases that enable cAMP levels to be artificially elevated within cells. We chart the evolution of sequences for selectively modifying protein-protein interactions that support cAMP signaling, and for driving cAMP sensors and manipulators to different subcellular locations. Importantly, these different genetically encoded tools can be applied synergistically, and we highlight notable instances that take advantage of this property. Finally, we consider prospects for extending the utility of the toolset to support further insights into the role of cAMP in health and disease.http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00164/fulladenylyl cyclasecAMPphosphodiesteraseAKAPPKA
spellingShingle Neha ePatel
Matthew G Gold
The genetically encoded tool set for investigating cAMP: more than the sum of its parts
Frontiers in Pharmacology
adenylyl cyclase
cAMP
phosphodiesterase
AKAP
PKA
title The genetically encoded tool set for investigating cAMP: more than the sum of its parts
title_full The genetically encoded tool set for investigating cAMP: more than the sum of its parts
title_fullStr The genetically encoded tool set for investigating cAMP: more than the sum of its parts
title_full_unstemmed The genetically encoded tool set for investigating cAMP: more than the sum of its parts
title_short The genetically encoded tool set for investigating cAMP: more than the sum of its parts
title_sort genetically encoded tool set for investigating camp more than the sum of its parts
topic adenylyl cyclase
cAMP
phosphodiesterase
AKAP
PKA
url http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00164/full
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