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Author Spotlight: Advancing Real-Time cAMP Detection in Cells Using cADDis Biosensor
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cAMP: From Long-Range Second Messenger to Nanodomain Signalling.
Nshunge Musheshe1, Martina Schmidt2, Manuela Zaccolo3
1Department of Molecular Pharmacology, University of Groningen, The Netherlands; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Trends in Pharmacological Sciences
|January 1, 2018
Summary
Cyclic adenosine monophosphate (cAMP) signals are compartmentalized within specific cell nanodomains, not just bulk cytoplasm. This discovery reframes understanding of cAMP
Area of Science:
- Cellular signaling
- Molecular biology
- Biochemistry
Background:
- The precise mechanisms by which cyclic adenosine monophosphate (cAMP) mediates hormone-specific cellular effects remain a long-standing question in cell biology.
- Classical models often consider cAMP as a freely diffusing second messenger throughout the cytosol.
Purpose of the Study:
- To investigate the spatial organization and compartmentalization of cAMP signals within intact cells.
- To elucidate the role of subcellular localization in determining cAMP-mediated cellular responses.
Main Methods:
- Utilized fluorescence resonance energy transfer (FRET)-based sensors for real-time imaging of cAMP dynamics.
- Employed high spatiotemporal resolution microscopy in intact cellular systems.
Main Results:
- Directly demonstrated that cAMP signals are compartmentalized within cells.
- Revealed previously unrecognized submicroscopic heterogeneity in intracellular cAMP distribution.
- Identified physiologically relevant cAMP signals occurring within confined nanodomains.
Conclusions:
- Emerging model suggests cAMP signal specificity is driven by compartmentalization within nanodomains.
- Challenges the traditional view of bulk cytosolic cAMP signaling.
- Provides a new conceptual framework for developing targeted cAMP-based therapeutics.
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