ArticlePloS one2017
Experimental and mathematical analysis of cAMP nanodomains.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 50 citations in OpenAlex.
- GPCR signaling via cAMP nanodomains.The Biochemical journal · 2025Review
- Intersection of GPCR trafficking and cAMP signaling at endomembranes.The Journal of cell biology · 2025Review
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Molecular Spies in Action: Genetically Encoded Fluorescent Biosensors Light up Cellular Signals.Chemical reviews · 2024Review
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Fluorescent biosensors illuminate the spatial regulation of cell signaling across scales.The Biochemical journal · 2023Review
- Fluorescent biosensor imaging meets deterministic mathematical modelling: quantitative investigation of signalling compartmentalization.The Journal of physiology · 2023Review
- Using the Proteomics Toolbox to Resolve Topology and Dynamics of Compartmentalized cAMP Signaling.International journal of molecular sciences · 2023Review
- A nuclear cAMP microdomain suppresses tumor growth by Hippo pathway inactivation.Cell reports · 2022Article
- Computational investigation of the dynamic control of cAMP signaling by PDE4 isoform types.Biophysical journal · 2022Article
- A multiscale model of the regulation of aquaporin 2 recycling.NPJ systems biology and applications · 2022Article
- Liquid-liquid phase separation: a principal organizer of the cell's biochemical activity architecture.Trends in pharmacological sciences · 2021Review
- Mechanisms of cAMP compartmentation in cardiac myocytes: experimental and computational approaches to understanding.The Journal of physiology · 2021Review
- Mitochondrial A-kinase anchoring proteins in cardiac ventricular myocytes.Physiological reports · 2021Article
- Review
- FluoSTEPs: Fluorescent biosensors for monitoring compartmentalized signaling within endogenous microdomains.Science advances · 2021Article
- Signaling Microdomains in the Spotlight: Visualizing Compartmentalized Signaling Using Genetically Encoded Fluorescent Biosensors.Annual review of pharmacology and toxicology · 2021Review
- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
- Article
- Phase Separation of a PKA Regulatory Subunit Controls cAMP Compartmentation and Oncogenic Signaling.Cell · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In their role as second messengers, cyclic nucleotides such as cAMP have a variety of intracellular effects. These complex tasks demand a highly organized orchestration of spatially and temporally confined cAMP action which should be best achieved by compartmentalization of the latter. A great body of evidence suggests that cAMP compartments may be established and maintained by cAMP degrading enzymes, e.g. phosphodiesterases (PDEs). However, the molecular and biophysical details of how PDEs can orchestrate cAMP gradients are entirely unclear. In this paper, using fusion proteins of cAMP FRET-sensors and PDEs in living cells, we provide direct experimental evidence that the cAMP concentration in the vicinity of an individual PDE molecule is below the detection limit of our FRET sensors (<100nM). This cAMP gradient persists in crude cytosol preparations. We developed mathematical models based on diffusion-reaction equations which describe the creation of nanocompartments around a single PDE molecule and more complex spatial PDE arrangements. The analytically solvable equations derived here explicitly determine how the capability of a single PDE, or PDE complexes, to create a nanocompartment depend on the cAMP degradation rate, the diffusive mobility of cAMP, and geometrical and topological parameters. We apply these generic models to our experimental data and determine the diffusive mobility and degradation rate of cAMP. The results obtained for these parameters differ by far from data in literature for free soluble cAMP interacting with PDE. Hence, restricted cAMP diffusion in the vincinity of PDE is necessary to create cAMP nanocompartments in cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.