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How cAMP generates hormone-specific effects has been debated for many decades. Fluorescence resonance energy transfer (FRET)-based sensors for cAMP allow real-time imaging of the second messenger in intact cells with high spatiotemporal resolution. This technology has made it possible to directly demonstrate that cAMP signals are compartmentalised. The details of such signal compartmentalisation are still being uncovered, and recent findings reveal a previously unsuspected submicroscopic heterogeneity of intracellular cAMP. A model is emerging where specificity depends on compartmentalisation and where the physiologically relevant signals are those that occur within confined nanodomains, rather than bulk changes in cytosolic cAMP. These findings subvert the classical notion of cAMP signalling and provide a new framework for the development of targeted therapeutic approaches.

Original publication

DOI

10.1016/j.tips.2017.11.006

Type

Journal article

Journal

Trends pharmacol sci

Publication Date

02/2018

Volume

39

Pages

209 - 222

Keywords

FRET imaging, G protein coupled receptors, cAMP, compartmentalisation, phosphodiesterases, protein kinase A