Evidence map›Paper›PMID 28497795›Full record

ArticleNature communications2017

A simple optogenetic MAPK inhibitor design reveals resonance between transcription-regulating circuitry and temporally-encoded inputs.

Raquel M Melero-Fernandez de Mera, Li-Li Li, Arkadiusz Popinigis, Katryna Cisek, Minna Tuittila, Leena Yadav, Andrius Serva, Michael J Courtney

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

15 citing papers in PubMed, 29 citations in OpenAlex.

  1. Cardiac optogenetics: shining light on signaling pathways.Pflugers Archiv : European journal of physiology · 2023
    Review
  2. Review
  3. Article
  4. Review
  5. Controlling the Covalent Reactivity of a Kinase Inhibitor with Light.Angewandte Chemie (International ed. in English) · 2021
    Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. 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

8 authors at 2 institutions in 1 country.

Raquel M Melero-Fernandez de MeraMolecular Signalling Laboratory, A.I. Virtanen Institute, University of Eastern Finland, Kuopio 70210, Finland.
Li-Li LiMolecular Signalling Laboratory, A.I. Virtanen Institute, University of Eastern Finland, Kuopio 70210, Finland.
Arkadiusz PopinigisNeuronal Signalling Laboratory, Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20520, Finland.
Katryna CisekMolecular Signalling Laboratory, A.I. Virtanen Institute, University of Eastern Finland, Kuopio 70210, Finland.
Minna TuittilaNeuronal Signalling Laboratory, Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20520, Finland.
Leena YadavMolecular Signalling Laboratory, A.I. Virtanen Institute, University of Eastern Finland, Kuopio 70210, Finland.
Andrius ServaMolecular Signalling Laboratory, A.I. Virtanen Institute, University of Eastern Finland, Kuopio 70210, Finland.
Michael J CourtneyMolecular Signalling Laboratory, A.I. Virtanen Institute, University of Eastern Finland, Kuopio 70210, Finland.ORCID 0000-0001-8693-3933
Åbo Akademi University · FIUniversity of Eastern Finland · FI

Funding

NOS1AP as a novel target for treating pathological painR01CA200417 · NCI · TRUSTEES OF INDIANA UNIVERSITY · PI COURTNEY, MICHAEL, HOHMANN, ANDREA GRACE · 2016 to 2020
$1.4M
NCI NIH HHS R01 CA200417
6 · The paper itself

Abstract

Engineering light-sensitive protein regulators has been a tremendous multidisciplinary challenge. Optogenetic regulators of MAPKs, central nodes of cellular regulation, have not previously been described. Here we present OptoJNKi, a light-regulated JNK inhibitor based on the AsLOV2 light-sensor domain using the ubiquitous FMN chromophore. OptoJNKi gene-transfer allows optogenetic applications, whereas protein delivery allows optopharmacology. Development of OptoJNKi suggests a design principle for other optically regulated inhibitors. From this, we generate Optop38i, which inhibits p38MAPK in intact illuminated cells. Neurons are known for interpreting temporally-encoded inputs via interplay between ion channels, membrane potential and intracellular calcium. However, the consequences of temporal variation of JNK-regulating trophic inputs, potentially resulting from synaptic activity and reversible cellular protrusions, on downstream targets are unknown. Using OptoJNKi, we reveal maximal regulation of c-Jun transactivation can occur at unexpectedly slow periodicities of inhibition depending on the inhibitor's subcellular location. This provides evidence for resonance in metazoan JNK-signalling circuits.

Indexed as

AnimalsAvenaCells, CulturedChlorocebus aethiopsCOS CellsDrug DesignFemaleHEK293 CellsHumansLightMaleMAP Kinase Signaling SystemNeuronsOptogeneticsp38 Mitogen-Activated Protein KinasesPhototropinsp38 Mitogen-Activated Protein KinasesPhototropinsProtein Kinase Inhibitors

Identifiers

PMID28497795
PMCPMC5437309
OpenAlexW2613406131

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.