ArticleNature2016
β-Arrestin biosensors reveal a rapid, receptor-dependent activation/deactivation cycle.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
What it found
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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.
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.
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Who cites it
109 citing papers in PubMed, 208 citations in OpenAlex.
- Atomic, structural and molecular insights into GPCR ligand binding and signalling.Nature reviews. Molecular cell biology · 2026Review
- Divergence of Melanopsin's Intrinsic Properties and Downstream Actions.bioRxiv : the preprint server for biology · 2026Article
- Configurational diversity of metabotropic glutamate receptor complexes with beta-arrestins.Nature communications · 2026Article
- Factors modulating the assembly of human βNature structural & molecular biology · 2026Article
- Constitutive activity of an atypical chemokine receptor revealed by inverse agonistic nanobodies.Nature communications · 2025Article
- A genetically encoded nanobody sensor reveals conformational diversity in β-arrestins orchestrated by distinct seven transmembrane receptors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Biased signalingActa pharmaceutica Sinica. B · 2025Review
- Isoprenaline shows unique kinase dependencies in stimulating βMolecular pharmacology · 2025Article
- Neurokinin 1 receptor inhibition alleviated mitochondrial dysfunctionActa pharmaceutica Sinica. B · 2025Article
- Constitutive activity of an atypical chemokine receptor revealed by inverse agonistic nanobodies.bioRxiv : the preprint server for biology · 2024Article
- Get Ready to Sharpen Your Tools: A Short Guide to Heterotrimeric G Protein Activity Biosensors.Molecular pharmacology · 2024Review
- Arrestins: A Small Family of Multi-Functional Proteins.International journal of molecular sciences · 2024Review
- Adrenoceptor Desensitization: Current Understanding of Mechanisms.Pharmacological reviews · 2024Review
- Computational drug development for membrane protein targets.Nature biotechnology · 2024Review
- Article
- Molecular insights into intrinsic transducer-coupling bias in the CXCR4-CXCR7 system.Nature communications · 2023Article
- Single hormone or synthetic agonist induces GProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Deafness-Associated ADGRV1 Mutation Impairs USH2A Stability through Improper Phosphorylation of WHRN and WDSUB1 Recruitment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Article
- Phosphorylation barcodes direct biased chemokine signaling at CXCR3.Cell chemical biology · 2023Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
(β-)Arrestins are important regulators of G-protein-coupled receptors (GPCRs). They bind to active, phosphorylated GPCRs and thereby shut off 'classical' signalling to G proteins, trigger internalization of GPCRs via interaction with the clathrin machinery and mediate signalling via 'non-classical' pathways. In addition to two visual arrestins that bind to rod and cone photoreceptors (termed arrestin1 and arrestin4), there are only two (non-visual) β-arrestin proteins (β-arrestin1 and β-arrestin2, also termed arrestin2 and arrestin3), which regulate hundreds of different (non-visual) GPCRs. Binding of these proteins to GPCRs usually requires the active form of the receptors plus their phosphorylation by G-protein-coupled receptor kinases (GRKs). The binding of receptors or their carboxy terminus as well as certain truncations induce active conformations of (β-)arrestins that have recently been solved by X-ray crystallography. Here we investigate both the interaction of β-arrestin with GPCRs, and the β-arrestin conformational changes in real time and in living human cells, using a series of fluorescence resonance energy transfer (FRET)-based β-arrestin2 biosensors. We observe receptor-specific patterns of conformational changes in β-arrestin2 that occur rapidly after the receptor-β-arrestin2 interaction. After agonist removal, these changes persist for longer than the direct receptor interaction. Our data indicate a rapid, receptor-type-specific, two-step binding and activation process between GPCRs and β-arrestins. They further indicate that β-arrestins remain active after dissociation from receptors, allowing them to remain at the cell surface and presumably signal independently. Thus, GPCRs trigger a rapid, receptor-specific activation/deactivation cycle of β-arrestins, which permits their active signalling.
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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.