Evidence map›Paper›PMID 24920824›Full record

ArticleMolecular biology of the cell2014

Subcellular optogenetic inhibition of G proteins generates signaling gradients and cell migration.

Patrick R O'Neill, N Gautam

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
–field-weighted citation impact
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

50 citing papers in PubMed.

  1. Monocyte Migration Emerges from a Divergent Chemokine Signaling Network.bioRxiv : the preprint server for biology · 2026
    Article
  2. Review
  3. Article
  4. Review
  5. Genetics-Based Targeting Strategies for Precise Neuromodulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  6. Opioid receptors reveal a discrete cellular mechanism of endosomal G protein activation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Review
  8. Article
  9. Selective optogenetic inhibition of GαProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  10. Article
  11. Cardiac optogenetics: shining light on signaling pathways.Pflugers Archiv : European journal of physiology · 2023
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Live Cell Imaging and Optogenetics-Based Assays for GPCR Activity.Methods in molecular biology (Clifton, N.J.) · 2021
    Article
  20. Review
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

2 authors.

Patrick R O'NeillDepartment of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110.
N GautamDepartment of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110 gautam@wustl.edu.

Funding

SIGNALING IN LIVING CELLSR01GM069027 · NIGMS · WASHINGTON UNIVERSITY · PI GAUTAM, NARASIMHAN · 2004 to 2016
$3.2M
G PROTEIN SUBUNIT FUNCTIONR01GM080558 · NIGMS · WASHINGTON UNIVERSITY · PI GAUTAM, NARASIMHAN · 2008 to 2011
$1.8M
OPTICAL CONTROL OF SINGLE CELL BEHAVIORR01GM107370 · NIGMS · WASHINGTON UNIVERSITY · PI GAUTAM, NARASIMHAN · 2014 to 2016
$1.1M
Mechanism and role of G-protein subunit translocation in cell signalingF32GM099351 · NIGMS · WASHINGTON UNIVERSITY · PI O'NEILL, PATRICK ROSS · 2011 to 2013
$155k
NIGMS NIH HHS F32 GM099351NIGMS NIH HHS GM069027NIGMS NIH HHS GM080558NIGMS NIH HHS GM099351NIGMS NIH HHS R01 GM069027NIGMS NIH HHS R01 GM080558NIGMS NIH HHS R01 GM107370
6 · The paper itself

Abstract

Cells sense gradients of extracellular cues and generate polarized responses such as cell migration and neurite initiation. There is static information on the intracellular signaling molecules involved in these responses, but how they dynamically orchestrate polarized cell behaviors is not well understood. A limitation has been the lack of methods to exert spatial and temporal control over specific signaling molecules inside a living cell. Here we introduce optogenetic tools that act downstream of native G protein-coupled receptor (GPCRs) and provide direct control over the activity of endogenous heterotrimeric G protein subunits. Light-triggered recruitment of a truncated regulator of G protein signaling (RGS) protein or a Gβγ-sequestering domain to a selected region on the plasma membrane results in localized inhibition of G protein signaling. In immune cells exposed to spatially uniform chemoattractants, these optogenetic tools allow us to create reversible gradients of signaling activity. Migratory responses generated by this approach show that a gradient of active G protein αi and βγ subunits is sufficient to generate directed cell migration. They also provide the most direct evidence so for a global inhibition pathway triggered by Gi signaling in directional sensing and adaptation. These optogenetic tools can be applied to interrogate the mechanistic basis of other GPCR-modulated cellular functions.

Indexed as

ChemotaxisSignal TransductionAnimalsCryptochromesG-Protein-Coupled Receptor Kinase 2GTP-Binding ProteinsGuanosine TriphosphateHeLa CellsHumansHydrolysisInositol PhosphatesMiceOptogeneticsProtein SubunitsProtein TransportCRY2 protein, humanCryptochromesG-Protein-Coupled Receptor Kinase 2GRK2 protein, humanGTP-Binding ProteinsGuanosine TriphosphateInositol PhosphatesProtein Subunits

Identifiers

PMID24920824
PMCPMC4116304

What OpenQuestion holds

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LicenceCC BY-NC-SA
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.