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Pharmacol Ther. 2014 Sep;143(3):295-304. doi: 10.1016/j.pharmthera.2014.03.008. Epub 2014 Apr 1.

cAMP signaling in subcellular compartments.

Author information

1
Department Of Physiology, Anatomy & Genetics, University of Oxford, UK.
2
Department Of Physiology, Anatomy & Genetics, University of Oxford, UK. Electronic address: manuela.zaccolo@dpag.ox.ac.uk.

Abstract

In the complex microcosm of a cell, information security and its faithful transmission are critical for maintaining internal stability. To achieve a coordinated response of all its parts to any stimulus the cell must protect the information received from potentially confounding signals. Physical segregation of the information transmission chain ensures that only the entities able to perform the encoded task have access to the relevant information. The cAMP intracellular signaling pathway is an important system for signal transmission responsible for the ancestral 'flight or fight' response and involved in the control of critical functions including frequency and strength of heart contraction, energy metabolism and gene transcription. It is becoming increasingly apparent that the cAMP signaling pathway uses compartmentalization as a strategy for coordinating the large number of key cellular functions under its control. Spatial confinement allows the formation of cAMP signaling "hot spots" at discrete subcellular domains in response to specific stimuli, bringing the information in proximity to the relevant effectors and their recipients, thus achieving specificity of action. In this report we discuss how the different constituents of the cAMP pathway are targeted and participate in the formation of cAMP compartmentalized signaling events. We illustrate a few examples of localized cAMP signaling, with a particular focus on the nucleus, the sarcoplasmic reticulum and the mitochondria. Finally, we discuss the therapeutic potential of interventions designed to perturb specific cAMP cascades locally.

KEYWORDS:

AKAPs; Compartmentalization; PDEs; PKA; Signaling; cAMP

PMID:
24704321
PMCID:
PMC4117810
DOI:
10.1016/j.pharmthera.2014.03.008
[Indexed for MEDLINE]
Free PMC Article

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