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Front Cell Neurosci. 2014 Oct 28;8:350. doi: 10.3389/fncel.2014.00350. eCollection 2014.

cAMP signaling microdomains and their observation by optical methods.

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Institute of Pharmacology and Toxicology, University of Würzburg Würzburg, Germany ; Bio-Imaging Center/Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg Würzburg, Germany.


The second messenger cyclic AMP (cAMP) is a major intracellular mediator of many hormones and neurotransmitters and regulates a myriad of cell functions, including synaptic plasticity in neurons. Whereas cAMP can freely diffuse in the cytosol, a growing body of evidence suggests the formation of cAMP gradients and microdomains near the sites of cAMP production, where cAMP signals remain apparently confined. The mechanisms responsible for the formation of such microdomains are subject of intensive investigation. The development of optical methods based on fluorescence resonance energy transfer (FRET), which allow a direct observation of cAMP signaling with high temporal and spatial resolution, is playing a fundamental role in elucidating the nature of such microdomains. Here, we will review the optical methods used for monitoring cAMP and protein kinase A (PKA) signaling in living cells, providing some examples of their application in neurons, and will discuss the major hypotheses on the formation of cAMP/PKA microdomains.


G protein-coupled receptor; cyclic AMP; fluorescence resonance energy transfer; neurons; signaling microdomain

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