ArticleThe Journal of biological chemistry2016
A G Protein-biased Designer G Protein-coupled Receptor Useful for Studying the Physiological Relevance of Gq/11-dependent Signaling Pathways.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Development of Mutant MBiochemistry · 2025Article
- Rational design of small-molecule responsive protein switches.Protein science : a publication of the Protein Society · 2023Review
- Mapping and targeted viral activation of pancreatic nerves in mice reveal their roles in the regulation of glucose metabolism.Nature biomedical engineering · 2022Article
- Chemogenetics of cell surface receptors: beyond genetic and pharmacological approaches.RSC chemical biology · 2022Review
- Monitoring TRPC7 Conformational Changes by BRET Following GPCR Activation.International journal of molecular sciences · 2022Article
- Chemogenetic approaches to identify metabolically important GPCR signaling pathways: Therapeutic implications.Journal of neurochemistry · 2021Review
- Amphetamines signal through intracellular TAAR1 receptors coupled to GαMolecular psychiatry · 2021Article
- Designer GPCRs as Novel Tools to Identify Metabolically Important Signaling Pathways.Frontiers in endocrinology · 2021Article
- Biased GPCR signaling: Possible mechanisms and inherent limitations.Pharmacology & therapeutics · 2020Review
- Optogenetic Techniques for Manipulating and Sensing G Protein-Coupled Receptor Signaling.Methods in molecular biology (Clifton, N.J.) · 2020Review
- DREADD Agonist 21 Is an Effective Agonist for Muscarinic-Based DREADDsACS pharmacology & translational science · 2018Article
- On the G protein-coupling selectivity of the native ABiochemical pharmacology · 2018Article
- Biased signalling: from simple switches to allosteric microprocessors.Nature reviews. Drug discovery · 2018Review
- Optogenetic approaches for dissecting neuromodulation and GPCR signaling in neural circuits.Current opinion in pharmacology · 2017Review
- Identification of key phosphorylation sites in PTH1R that determine arrestin3 binding and fine-tune receptor signaling.The Biochemical journal · 2016Article
- Use of Designer G Protein-Coupled Receptors to Dissect Metabolic Pathways.Trends in endocrinology and metabolism: TEM · 2016Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Designerreceptorsexclusivelyactivated by adesignerdrug (DREADDs) are clozapine-N-oxide-sensitive designer G protein-coupled receptors (GPCRs) that have emerged as powerful novel chemogenetic tools to study the physiological relevance of GPCR signaling pathways in specific cell types or tissues. Like endogenous GPCRs, clozapine-N-oxide-activated DREADDs do not only activate heterotrimeric G proteins but can also trigger β-arrestin-dependent (G protein-independent) signaling. To dissect the relative physiological relevance of G protein-mediatedversusβ-arrestin-mediated signaling in different cell types or physiological processes, the availability of G protein- and β-arrestin-biased DREADDs would be highly desirable. In this study, we report the development of a mutationally modified version of a non-biased DREADD derived from the M3muscarinic receptor that can activate Gq/11with high efficacy but lacks the ability to interact with β-arrestins. We also demonstrate that this novel DREADD is activein vivoand that cell type-selective expression of this new designer receptor can provide novel insights into the physiological roles of G protein (Gq/11)-dependentversusβ-arrestin-dependent signaling in hepatocytes. Thus, this novel Gq/11-biased DREADD represents a powerful new tool to study the physiological relevance of Gq/11-dependent signaling in distinct tissues and cell types, in the absence of β-arrestin-mediated cellular effects. Such studies should guide the development of novel classes of functionally biased ligands that show high efficacy in various pathophysiological conditions but display a reduced incidence of side effects.
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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.