ArticleProceedings of the National Academy of Sciences of the United States of America2007
Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,282 papers.
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.
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.
Who cites it
1,282 citing papers in PubMed, 2,075 citations in OpenAlex.
- Substrate-specific regulation of the mTORC1 pathway by G protein-coupled receptors.The Biochemical journal · 2026Article
- Gq Signaling in Microglia Triggers Interferon Responses and Improves Outcome After Ischemic Stroke.Glia · 2026Article
- Article
- Off-target effects of DREADD ligands revealed by an anesthesia emergence paradigm in mice.Cell reports methods · 2026Article
- Differential contributions of striatal dopaminergic pathways to visuomotor conditional learning.Psychopharmacology · 2026Article
- Anesthesia unconsciousness recruits dynamic parabrachial activity within a distributed brain-wide ensemble.bioRxiv : the preprint server for biology · 2026Article
- MicroRNA-sensing plasmid system for dynamic control of functional ion channel expression.Molecular therapy. Nucleic acids · 2026Article
- Calbindin stratifies midbrain dopaminergic neurons governing distinct aspects of locomotion.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- A suite of engineered mice for interrogating psychedelic drug actions.Nature neuroscience · 2026Article
- Activation of GScience advances · 2026Article
- Sleep circuit modulation: from animal models to human translation.Brain : a journal of neurology · 2026Review
- Overview of the DREADDs chemogenetics and the patent landscape of their actuators.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Chemogenetic Activation of GFASEB bioAdvances · 2026Article
- Altered GScience advances · 2026Article
- Next-generation chemogenetic inhibition using a brain-permeant non-prescription agent.Signal transduction and targeted therapy · 2026Article
- PIPbioRxiv : the preprint server for biology · 2026Article
- A synaptic locus of song learning.Nature · 2026Article
- Understanding nerve-tumor interactions: From basic biology to therapeutic innovation.Genes & diseases · 2026Review
- Article
1,222 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
We evolved muscarinic receptors in yeast to generate a family of G protein-coupled receptors (GPCRs) that are activated solely by a pharmacologically inert drug-like and bioavailable compound (clozapine-N-oxide). Subsequent screening in human cell lines facilitated the creation of a family of muscarinic acetylcholine GPCRs suitable for in vitro and in situ studies. We subsequently created lines of telomerase-immortalized human pulmonary artery smooth muscle cells stably expressing all five family members and found that each one faithfully recapitulated the signaling phenotype of the parent receptor. We also expressed a G(i)-coupled designer receptor in hippocampal neurons (hM(4)D) and demonstrated its ability to induce membrane hyperpolarization and neuronal silencing. We have thus devised a facile approach for designing families of GPCRs with engineered ligand specificities. Such reverse-engineered GPCRs will prove to be powerful tools for selectively modulating signal-transduction pathways in vitro and in vivo.
Indexed as
Identifiers
What OpenQuestion holds
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.