ArticleNature2013
Conformational biosensors reveal GPCR signalling from endosomes.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 468 papers.
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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.
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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.
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Who cites it
468 citing papers in PubMed, 835 citations in OpenAlex.
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- Spatial control of parathyroid hormone receptor-1 signaling dictates ligand-specific biological outcomes.Signal transduction and targeted therapy · 2026Article
- Endosomes: An underappreciated player in cell signal transduction.Fundamental research · 2026Review
- Inhibitory probes for spatiotemporal analysis of GαNature chemical biology · 2026Article
- AKAP6β-a conductor in the orchestra of pathological cardiomyocyte gene transcription.Molecular pharmacology · 2026Review
- Arrestins as programmable integrators of GPCR signaling: structural microstates, spatiotemporal logic, and therapeutic control.Cell discovery · 2026Review
- Intracellular protein binders for imaging, control and future therapeutics.Nature biomedical engineering · 2026Review
- Development of pH-Sensitive β‑Adrenergic Receptor Antagonists.ACS pharmacology & translational science · 2026Article
- Mechanisms and Manifestations of Ligand Bias in Signaling: Focus on Receptor Tyrosine Kinases.Chemical reviews · 2026Review
- Oncogenic Gα signaling requires AP-3-dependent recruitment to the endolysosomal compartment.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The working lives of neuronal 5-HTRSC chemical biology · 2026Review
- The Fragmented Nature of Biosensor Development: Challenges and Paths to Mitigation.Biosensors · 2026Review
- Biased signaling of β2-adrenergic receptor in physiological and pathological states.Cellular & molecular biology letters · 2026Review
- Hypervariable loop profiling decodes sequence determinants of antibody stability.Nature structural & molecular biology · 2026Article
- Tool antibody fragments reveal multiple conformations of the rhodopsin-Gi signaling complex.Biophysical journal · 2026Article
- Cooperative Control of Arrestin Activation By Membrane Lipids And Phosphorylation Barcodes.bioRxiv : the preprint server for biology · 2026Article
- Tiny tools closing the gap: nanobodies in research and therapy.Function (Oxford, England) · 2026Review
- G protein GαThe Journal of biological chemistry · 2026Article
- GPCR-selective effects of endocytosis on cellular signaling through the cAMP/PKA cascade.The Journal of biological chemistry · 2026Article
- Nanoparticle-mediated antagonism of sustained endosomal signaling of the calcitonin receptor-like receptor provides enhanced and persistent relief of oral cancer pain.Biomaterials · 2026Article
408 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
A long-held tenet of molecular pharmacology is that canonical signal transduction mediated by G-protein-coupled receptor (GPCR) coupling to heterotrimeric G proteins is confined to the plasma membrane. Evidence supporting this traditional view is based on analytical methods that provide limited or no subcellular resolution. It has been subsequently proposed that signalling by internalized GPCRs is restricted to G-protein-independent mechanisms such as scaffolding by arrestins, or GPCR activation elicits a discrete form of persistent G protein signalling, or that internalized GPCRs can indeed contribute to the acute G-protein-mediated response. Evidence supporting these various latter hypotheses is indirect or subject to alternative interpretation, and it remains unknown if endosome-localized GPCRs are even present in an active form. Here we describe the application of conformation-specific single-domain antibodies (nanobodies) to directly probe activation of the β2-adrenoceptor, a prototypical GPCR, and its cognate G protein, Gs (ref. 12), in living mammalian cells. We show that the adrenergic agonist isoprenaline promotes receptor and G protein activation in the plasma membrane as expected, but also in the early endosome membrane, and that internalized receptors contribute to the overall cellular cyclic AMP response within several minutes after agonist application. These findings provide direct support for the hypothesis that canonical GPCR signalling occurs from endosomes as well as the plasma membrane, and suggest a versatile strategy for probing dynamic conformational change in vivo.
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Registered trials
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.