ArticlePloS one2007
Modifying ligand-induced and constitutive signaling of the human 5-HT4 receptor.
Article in PloS one, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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.
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
30 citing papers in PubMed, 47 citations in OpenAlex.
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- Unraveling the Neural Circuits: Techniques, Opportunities and Challenges in Epilepsy Research.Cellular and molecular neurobiology · 2024Review
- Cardiac Roles of Serotonin (5-HT) and 5-HT-Receptors in Health and Disease.International journal of molecular sciences · 2023Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Advances in Models of Fibrous Dysplasia/McCune-Albright Syndrome.Frontiers in endocrinology · 2019Review
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- Gs/Gi Regulation of Bone Cell Differentiation: Review and Insights from Engineered Receptors.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2016Review
- Optogenetic and Chemogenetic Approaches for Studying Astrocytes and Gliotransmitters.Experimental neurobiology · 2016Review
- Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory.Nature neuroscience · 2015Article
- Minireview: complexity of hematopoietic stem cell regulation in the bone marrow microenvironment.Molecular endocrinology (Baltimore, Md.) · 2014Review
- Employing novel animal models in the design of clinically efficacious GPCR ligands.Current opinion in cell biology · 2014Review
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- A hybrid structural approach to analyze ligand binding by the serotonin type 4 receptor (5-HT4).Molecular & cellular proteomics : MCP · 2013Article
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- Activated Gs signaling in osteoblastic cells alters the hematopoietic stem cell niche in mice.Blood · 2012Article
- An siRNA screen in pancreatic beta cells reveals a role for Gpr27 in insulin production.PLoS genetics · 2012Article
- Developing chemical genetic approaches to explore G protein-coupled receptor function: validation of the use of a receptor activated solely by synthetic ligand (RASSL).Molecular pharmacology · 2011Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
G protein-coupled receptors (GPCRs) signal through a limited number of G-protein pathways and play crucial roles in many biological processes. Studies of their in vivo functions have been hampered by the molecular and functional diversity of GPCRs and the paucity of ligands with specific signaling effects. To better compare the effects of activating different G-protein signaling pathways through ligand-induced or constitutive signaling, we developed a new series of RASSLs (receptors activated solely by synthetic ligands) that activate different G-protein signaling pathways. These RASSLs are based on the human 5-HT(4b) receptor, a GPCR with high constitutive G(s) signaling and strong ligand-induced G-protein activation of the G(s) and G(s/q) pathways. The first receptor in this series, 5-HT(4)-D(100)A or Rs1 (RASSL serotonin 1), is not activated by its endogenous agonist, serotonin, but is selectively activated by the small synthetic molecules GR113808, GR125487, and RO110-0235. All agonists potently induced G(s) signaling, but only a few (e.g., zacopride) also induced signaling via the G(q) pathway. Zacopride-induced G(q) signaling was enhanced by replacing the C-terminus of Rs1 with the C-terminus of the human 5-HT(2C) receptor. Additional point mutations (D(66)A and D(66)N) blocked constitutive G(s) signaling and lowered ligand-induced G(q) signaling. Replacing the third intracellular loop of Rs1 with that of human 5-HT(1A) conferred ligand-mediated G(i) signaling. This G(i)-coupled RASSL, Rs1.3, exhibited no measurable signaling to the G(s) or G(q) pathway. These findings show that the signaling repertoire of Rs1 can be expanded and controlled by receptor engineering and drug selection.
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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.