Evidence map›Paper›PMID 23264735›Full record

ArticleJournal of cell science2013

Separate roles of PKA and EPAC in renal function unraveled by the optogenetic control of cAMP levels in vivo.

Marina Efetova, Linda Petereit, Kamil Rosiewicz, Gayle Overend, Florian Haußig, Bernhard T Hovemann, Pablo Cabrero, Julian A T Dow, Martin Schwärzel

Open access · bronzeAbstract read
In one paragraph

Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.4field-weighted citation impact, top 23% 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

20 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. The V-type HProceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  5. Article
  6. Article
  7. Article
  8. The Drosophila Malpighian tubule as a model for mammalian tubule function.Current opinion in nephrology and hypertension · 2019
    Review
  9. Article
  10. Review
  11. Null EPAC mutants reveal a sequential order of versatile cAMP effects duringLearning & memory (Cold Spring Harbor, N.Y.) · 2017
    Article
  12. Article
  13. Article
  14. Article
  15. Two inwardly rectifying potassium channels, Irk1 and Irk2, play redundant roles in Drosophila renal tubule function.American journal of physiology. Regulatory, integrative and comparative physiology · 2015
    Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Engineering adenylate cyclases regulated by near-infrared window light.Proceedings of the National Academy of Sciences of the United States of America · 2014
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Marina EfetovaInstitute for Biology/Genetics, Free University Berlin, D-14195 Berlin, Germany.
Linda Petereit
Kamil Rosiewicz
Gayle Overend
Florian Haußig
Bernhard T Hovemann
Pablo Cabrero
Julian A T Dow
Martin Schwärzel
Freie Universität Berlin · DEUniversity of Glasgow · GBRuhr University Bochum · DE

Funding

Tools to conditionally regulate intracellular signaling pathways in vivoR01MH086415 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI ABEL, EDWIN TED G. · 2009 to 2013
$2.3M
Biotechnology and Biological Sciences Research Council BB/F021240/1Biotechnology and Biological Sciences Research Council BB/H001042/1Biotechnology and Biological Sciences Research Council BB/J002143/1NIMH NIH HHS 1R0MH086415
6 · The paper itself

Abstract

Cyclic AMP (cAMP) is a ubiquitous second messenger that regulates a variety of essential processes in diverse cell types, functioning via cAMP-dependent effectors such as protein kinase A (PKA) and/or exchange proteins directly activated by cAMP (EPAC). In an intact tissue it is difficult to separate the contribution of each cAMP effector in a particular cell type using genetic or pharmacological approaches alone. We, therefore, utilized optogenetics to overcome the difficulties associated with examining a multicellular tissue. The transgenic photoactive adenylyl cyclase bPAC can be activated to rapidly and reversibly generate cAMP pulses in a cell-type-specific manner. This optogenetic approach to cAMP manipulation was validated in vivo using GAL4-driven UAS-bPAC in a simple epithelium, the Drosophila renal (Malpighian) tubules. As bPAC was expressed under the control of cell-type-specific promoters, each cAMP signal could be directed to either the stellate or principal cells, the two major cell types of the Drosophila renal tubule. By combining the bPAC transgene with genetic and pharmacological manipulation of either PKA or EPAC it was possible to investigate the functional impact of PKA and EPAC independently of each other. The results of this investigation suggest that both PKA and EPAC are involved in cAMP sensing, but are engaged in very different downstream physiological functions in each cell type: PKA is necessary for basal secretion in principal cells only, and for stimulated fluid secretion in stellate cells only. By contrast, EPAC is important in stimulated fluid secretion in both cell types. We propose that such optogenetic control of cellular cAMP levels can be applied to other systems, for example the heart or the central nervous system, to investigate the physiological impact of cAMP-dependent signaling pathways with unprecedented precision.

Indexed as

Adenylyl CyclasesAnimalsAnimals, Genetically ModifiedCell CommunicationCell LineCyclic AMPCyclic AMP-Dependent Protein KinasesDrosophila melanogasterDrosophila ProteinsEpithelial CellsGuanine Nucleotide Exchange FactorsMalpighian TubulesOptogeneticsOrgan SpecificitySignal TransductionAdenylyl CyclasesCyclic AMPCyclic AMP-Dependent Protein KinasesDrosophila ProteinsEpac protein, DrosophilaGuanine Nucleotide Exchange Factors

Identifiers

PMID23264735
PMCPMC3619808
OpenAlexW1985002158

What OpenQuestion holds

Textmetadata
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.