Evidence map›Paper›PMID 27879340›Full record

ArticleMolecular pharmacology2017

G Protein-Coupled Receptor Endocytosis Confers Uniformity in Responses to Chemically Distinct Ligands.

Nikoleta G Tsvetanova, Michelle Trester-Zedlitz, Billy W Newton, Daniel P Riordan, Aparna B Sundaram, Jeffrey R Johnson, Nevan J Krogan, Mark von Zastrow

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.7field-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

19 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
  2. Class A and B GPCRs trigger rapid GαCommunications biology · 2025
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  5. The psychosis risk factorbioRxiv : the preprint server for biology · 2023
    Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. A cellular perspective of bias at G protein-coupled receptors.Protein science : a publication of the Protein Society · 2020
    Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. 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 4 institutions in 1 country.

Nikoleta G TsvetanovaDepartment of Psychiatry (N.G.T., M.T.-Z., M.Z.), Department of Cellular and Molecular Pharmacology (M.Z.), California Institute for Quantitative Biosciences (B.W.N., J.R.J., N.J.K.), and Lung Biology Center, Department of Medicine (A.B.S.), University of California, San Francisco, San Francisco, California; J. David Gladstone Institute, San Francisco, California (N.J.K.); and Department of Biochemistry, Stanford University, Stanford, California (D.P.R.) Nikoleta.Tsvetanova@ucsf.edu.
Michelle Trester-ZedlitzDepartment of Psychiatry (N.G.T., M.T.-Z., M.Z.), Department of Cellular and Molecular Pharmacology (M.Z.), California Institute for Quantitative Biosciences (B.W.N., J.R.J., N.J.K.), and Lung Biology Center, Department of Medicine (A.B.S.), University of California, San Francisco, San Francisco, California; J. David Gladstone Institute, San Francisco, California (N.J.K.); and Department of Biochemistry, Stanford University, Stanford, California (D.P.R.).
Billy W NewtonDepartment of Psychiatry (N.G.T., M.T.-Z., M.Z.), Department of Cellular and Molecular Pharmacology (M.Z.), California Institute for Quantitative Biosciences (B.W.N., J.R.J., N.J.K.), and Lung Biology Center, Department of Medicine (A.B.S.), University of California, San Francisco, San Francisco, California; J. David Gladstone Institute, San Francisco, California (N.J.K.); and Department of Biochemistry, Stanford University, Stanford, California (D.P.R.).
Daniel P RiordanDepartment of Psychiatry (N.G.T., M.T.-Z., M.Z.), Department of Cellular and Molecular Pharmacology (M.Z.), California Institute for Quantitative Biosciences (B.W.N., J.R.J., N.J.K.), and Lung Biology Center, Department of Medicine (A.B.S.), University of California, San Francisco, San Francisco, California; J. David Gladstone Institute, San Francisco, California (N.J.K.); and Department of Biochemistry, Stanford University, Stanford, California (D.P.R.).
Aparna B SundaramDepartment of Psychiatry (N.G.T., M.T.-Z., M.Z.), Department of Cellular and Molecular Pharmacology (M.Z.), California Institute for Quantitative Biosciences (B.W.N., J.R.J., N.J.K.), and Lung Biology Center, Department of Medicine (A.B.S.), University of California, San Francisco, San Francisco, California; J. David Gladstone Institute, San Francisco, California (N.J.K.); and Department of Biochemistry, Stanford University, Stanford, California (D.P.R.).
Jeffrey R JohnsonDepartment of Psychiatry (N.G.T., M.T.-Z., M.Z.), Department of Cellular and Molecular Pharmacology (M.Z.), California Institute for Quantitative Biosciences (B.W.N., J.R.J., N.J.K.), and Lung Biology Center, Department of Medicine (A.B.S.), University of California, San Francisco, San Francisco, California; J. David Gladstone Institute, San Francisco, California (N.J.K.); and Department of Biochemistry, Stanford University, Stanford, California (D.P.R.).
Nevan J KroganDepartment of Psychiatry (N.G.T., M.T.-Z., M.Z.), Department of Cellular and Molecular Pharmacology (M.Z.), California Institute for Quantitative Biosciences (B.W.N., J.R.J., N.J.K.), and Lung Biology Center, Department of Medicine (A.B.S.), University of California, San Francisco, San Francisco, California; J. David Gladstone Institute, San Francisco, California (N.J.K.); and Department of Biochemistry, Stanford University, Stanford, California (D.P.R.).
Mark von ZastrowDepartment of Psychiatry (N.G.T., M.T.-Z., M.Z.), Department of Cellular and Molecular Pharmacology (M.Z.), California Institute for Quantitative Biosciences (B.W.N., J.R.J., N.J.K.), and Lung Biology Center, Department of Medicine (A.B.S.), University of California, San Francisco, San Francisco, California; J. David Gladstone Institute, San Francisco, California (N.J.K.); and Department of Biochemistry, Stanford University, Stanford, California (D.P.R.).
University of California, San Francisco · USQB3 · USStanford University · USGladstone Institutes · US

Funding

X-ray Screening and Rapid Structure DeterminationP50GM082250 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KROGAN, NEVAN J · 2007 to 2018
$48.8M
Rewiring Therapeutic Cells: User-Controlled T Cells and Stem CellsP50GM081879 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 2010 to 2017
$19.0M
The Presynaptic Vesicle Cycle for the Slow Acting Neurotransmitter SecretionP01DA010154 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI EDWARDS, ROBERT H, KREITZER, ANATOL · 1995 to 2016
$14.7M
PROTEINS REGULATING ENDOCYTOSIS OF OPIOID RECEPTORSR01DA012864 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mark E Von Zastrow · 2000 to 2026
$7.9M
Membrane Trafficking of Opioid and Adrenergic ReceptorsR01DA010711 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VONZASTROW, MARK E · 2014 to 2023
$4.6M
MEMBRANE TRAFFICKING OF OPIOID RECEPTORSR37DA010711 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VONZASTROW, MARK E · 2004 to 2013
$3.1M
Physical and Genetic Interaction Landscape of the Tyrosine KinomeR01GM107671 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BANDYOPADHYAY, SOURAV · 2014 to 2017
$1.8M
Role of Human Chymase in Smooth Muscle Contraction in AsthmaK08HL124049 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SUNDARAM, APARNA BALA · 2015 to 2019
$822k
Functional specialization of compartmentalized beta2-adrenergic signaling in neuronsR00MH109633 · NIMH · DUKE UNIVERSITY · PI TSVETANOVA, NIKOLETA GEORGIEVA · 2018 to 2020
$743k
MEMBRANE TRAFFICKING OF OPIOID RECEPTORSR29DA010711 · NIDA · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI VON ZASTROW, MARK E. · 1997 to 2003
$413k
Functional specialization of compartmentalized beta2-adrenergic signaling in neuronsK99MH109633 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI TSVETANOVA, NIKOLETA GEORGIEVA · 2016 to 2017
$242k
NHLBI NIH HHS K08 HL124049NIDA NIH HHS P01 DA010154NIDA NIH HHS R01 DA010711NIDA NIH HHS R01 DA012864NIDA NIH HHS R29 DA010711NIDA NIH HHS R37 DA010711NIGMS NIH HHS P50 GM081879NIGMS NIH HHS P50 GM082250NIGMS NIH HHS R01 GM107671NIMH NIH HHS K99 MH109633NIMH NIH HHS R00 MH109633
6 · The paper itself

Abstract

The ability of chemically distinct ligands to produce different effects on the same G protein-coupled receptor (GPCR) has interesting therapeutic implications, but, if excessively propagated downstream, would introduce biologic noise compromising cognate ligand detection. We asked whether cells have the ability to limit the degree to which chemical diversity imposed at the ligand-GPCR interface is propagated to the downstream signal. We carried out an unbiased analysis of the integrated cellular response elicited by two chemically and pharmacodynamically diverse β-adrenoceptor agonists, isoproterenol and salmeterol. We show that both ligands generate an identical integrated response, and that this stereotyped output requires endocytosis. We further demonstrate that the endosomal β2-adrenergic receptor signal confers uniformity on the downstream response because it is highly sensitive and saturable. Based on these findings, we propose that GPCR signaling from endosomes functions as a biologic noise filter to enhance reliability of cognate ligand detection.

Indexed as

EndocytosisEndosomesHEK293 CellsHumansIsoproterenolLigandsMass SpectrometryModels, BiologicalOligonucleotide Array Sequence AnalysisPhosphoproteinsPhosphorylationProteomeProteomicsReceptors, Adrenergic, beta-2Receptors, G-Protein-CoupledSalmeterol XinafoateIsoproterenolLigandsPhosphoproteinsProteomeReceptors, Adrenergic, beta-2Receptors, G-Protein-CoupledSalmeterol Xinafoate

Identifiers

PMID27879340
PMCPMC5267521
OpenAlexW2552869352

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.