ArticleScience signaling2016
Dominant-negative Gα subunits are a mechanism of dysregulated heterotrimeric G protein signaling in human disease.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Inhibitory probes for spatiotemporal analysis of GαNature chemical biology · 2026Article
- Nf2/FGFR1/AKT axis directs cranial neural crest-derived skull morphogenesis via collagen synthesis and trafficking.JCI insight · 2025Article
- Dominant Gα mutations in human disease: unifying mechanisms and treatment strategies.EMBO molecular medicine · 2025Review
- Cyclic peptide inhibitors function as molecular glues to stabilize Gq/11 heterotrimers.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Gq/11 family of Gα subunits is necessary and sufficient for lower jaw development.Development (Cambridge, England) · 2025Article
- TheFrontiers in medicine · 2025Review
- Germline mutations in a G protein identify signaling cross-talk in T cells.Science (New York, N.Y.) · 2024Article
- Get Ready to Sharpen Your Tools: A Short Guide to Heterotrimeric G Protein Activity Biosensors.Molecular pharmacology · 2024Review
- Growth factor-dependent phosphorylation of GαScience signaling · 2024Article
- Direct interrogation of context-dependent GPCR activity with a universal biosensor platform.Cell · 2024Article
- Direct interrogation of context-dependent GPCR activity with a universal biosensor platform.bioRxiv : the preprint server for biology · 2024Article
- Molecular annotation of G protein variants in a neurological disorder.Cell reports · 2023Article
- Endothelin signaling in development.Development (Cambridge, England) · 2023Review
- Detecting GPCR Signals With Optical Biosensors of Gα-GTP in Cell Lines and Primary Cell Cultures.Current protocols · 2023Article
- Mandibulofacial dysostosis with alopecia results from ETAR gain-of-function mutations via allosteric effects on ligand binding.The Journal of clinical investigation · 2023Article
- Auriculocondylar syndrome 2 results from the dominant-negative action of PLCB4 variants.Disease models & mechanisms · 2022Article
- Prenatal diagnosis of auriculocondylar syndrome with a novel missense variant of GNAI3: a case report.BMC pregnancy and childbirth · 2021Article
- Article
- Revealing the Activity of Trimeric G-proteins in Live Cells with a Versatile Biosensor Design.Cell · 2020Article
- Characterizing how probioticBone reports · 2019Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Auriculo-condylar syndrome (ACS), a rare condition that impairs craniofacial development, is caused by mutations in a G protein-coupled receptor (GPCR) signaling pathway. In mice, disruption of signaling by the endothelin type A receptor (ET(A)R), which is mediated by the G protein (heterotrimeric guanine nucleotide-binding protein) subunit Gα(q/11) and subsequently phospholipase C (PLC), impairs neural crest cell differentiation that is required for normal craniofacial development. Some ACS patients have mutations inGNAI3, which encodes Gα(i3), but it is unknown whether this G protein has a role within the ET(A)R pathway. We used a Xenopus model of vertebrate development, in vitro biochemistry, and biosensors of G protein activity in mammalian cells to systematically characterize the phenotype and function of all known ACS-associated Gα(i3) mutants. We found that ACS-associated mutations in GNAI3 produce dominant-negative Gα(i3) mutant proteins that couple to ET(A)R but cannot bind and hydrolyze guanosine triphosphate, resulting in the prevention of endothelin-mediated activation of Gα(q/11) and PLC. Thus, ACS is caused by functionally dominant-negative mutations in a heterotrimeric G protein subunit.
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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.