Evidence map›Paper›PMID 32846156›Full record

ArticleCell2020

Optical Mapping of cAMP Signaling at the Nanometer Scale.

Andreas Bock, Paolo Annibale, Charlotte Konrad, Annette Hannawacker, Selma E Anton, Isabella Maiellaro, Ulrike Zabel, Sivaraj Sivaramakrishnan, Martin Falcke, Martin J Lohse

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 116 papers.

0numbers the graph read from it
0cells of the map it votes in
116citing papers in PubMed
10.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

116 citing papers in PubMed, 186 citations in OpenAlex.

  1. Review
  2. Article
  3. Regulation of Translation by PKA Signaling Pathway.International journal of molecular sciences · 2026
    Review
  4. Directly adopting inverse biosensors to image live cell enzyme activities in nanodomains.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. ATP8B1 Deficiency Causes Phosphodiesterase 4-Mediated Glucagon Resistance and Impaired Gluconeogenesis in Mouse and Human Liver.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Article
  14. Signaling by intracellular βCell reports · 2025
    Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

56 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Andreas BockMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Str. 10, 13125 Berlin, Germany; Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany. Electronic address: andreas.bock@mdc-berlin.de.
Paolo AnnibaleMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Str. 10, 13125 Berlin, Germany; Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany.
Charlotte KonradMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Str. 10, 13125 Berlin, Germany; Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany.
Annette HannawackerInstitute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany.
Selma E AntonMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Str. 10, 13125 Berlin, Germany; Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany.
Isabella MaiellaroInstitute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany.
Ulrike ZabelInstitute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany.
Sivaraj SivaramakrishnanDepartment of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
Martin FalckeMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Str. 10, 13125 Berlin, Germany; Department of Physics, Humboldt University, Newtonstr. 15, 12489 Berlin, Germany.
Martin J LohseMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Str. 10, 13125 Berlin, Germany; Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany; Institute for Chemistry and Biochemistry, Free University, Takustr. 3, 14195 Berlin, Germany; ISAR Bioscience Institute, 82152 Munich/Planegg, Germany. Electronic address: m.lohse@mdc-berlin.de.
Max Delbrück Center · DEUniversity of Würzburg · DEUniversity of Minnesota · US

Funding

Emergent cellular functions of GPCRs and myosinsR35GM126940 · NIGMS · UNIVERSITY OF MINNESOTA · PI Sivaraj Sivaramakrishnan · 2018 to 2026
$3.8M
NIGMS NIH HHS R35 GM126940
6 · The paper itself

Abstract

Cells relay a plethora of extracellular signals to specific cellular responses by using only a few second messengers, such as cAMP. To explain signaling specificity, cAMP-degrading phosphodiesterases (PDEs) have been suggested to confine cAMP to distinct cellular compartments. However, measured rates of fast cAMP diffusion and slow PDE activity render cAMP compartmentalization essentially impossible. Using fluorescence spectroscopy, we show that, contrary to earlier data, cAMP at physiological concentrations is predominantly bound to cAMP binding sites and, thus, immobile. Binding and unbinding results in largely reduced cAMP dynamics, which we term "buffered diffusion." With a large fraction of cAMP being buffered, PDEs can create nanometer-size domains of low cAMP concentrations. Using FRET-cAMP nanorulers, we directly map cAMP gradients at the nanoscale around PDE molecules and the areas of resulting downstream activation of cAMP-dependent protein kinase (PKA). Our study reveals that spatiotemporal cAMP signaling is under precise control of nanometer-size domains shaped by PDEs that gate activation of downstream effectors.

Indexed as

Signal TransductionComputer SimulationCyclic AMPCyclic AMP-Dependent Protein KinasesCytoplasmFluorescence Resonance Energy TransferHEK293 CellsHumansModels, MolecularPhosphoric Diester HydrolasesProtein BindingProtein DomainsRecombinant ProteinsSingle-Cell AnalysisSpatio-Temporal AnalysisSpectrometry, FluorescenceCyclic AMPCyclic AMP-Dependent Protein KinasesPhosphoric Diester HydrolasesRecombinant Proteinsbuffered diffusioncell signalingcompartmentationcyclic AMPfluorescence fluctuation spectroscopyFRET biosensorsG protein-coupled receptorsnanodomainsphosphodiesteraseprotein kinase A4

Identifiers

PMID32846156
PMCPMC7984459
OpenAlexW3080485174

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

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.