ArticleProceedings of the National Academy of Sciences of the United States of America2006
Some G protein heterotrimers physically dissociate in living cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 138 citations in OpenAlex.
- G protein diffusion states reveal receptor binding dynamics at single-molecule scale.Cell chemical biology · 2026Article
- Inhibitory probes for spatiotemporal analysis of GαNature chemical biology · 2026Article
- Going Rogue: Mechanisms, Regulation, and Roles of Mutationally Activated GMolecular pharmacology · 2024Review
- A molecular mechanism to diversify CaNature communications · 2024Article
- Get Ready to Sharpen Your Tools: A Short Guide to Heterotrimeric G Protein Activity Biosensors.Molecular pharmacology · 2024Review
- Specific pharmacological and GNature communications · 2024Article
- Heterotrimeric G protein signaling without GPCRs: The Gα-binding-and-activating (GBA) motif.The Journal of biological chemistry · 2024Review
- Atypical Chemokine Receptor 3 "Senses" CXC Chemokine Receptor 4 Activation Through GPCR Kinase Phosphorylation.Molecular pharmacology · 2023Article
- Atypical Chemokine Receptor 3 'Senses' CXC Chemokine Receptor 4 Activation Through GPCR Kinase Phosphorylation.bioRxiv : the preprint server for biology · 2023Article
- OZITX, a pertussis toxin-like protein for occluding inhibitory G protein signalling including GαCommunications biology · 2022Article
- Heterotrimeric G Proteins in Plants: Canonical and Atypical Gα Subunits.International journal of molecular sciences · 2021Review
- Inhibitory signaling in mammalian olfactory transduction potentially mediated by GαMolecular and cellular neurosciences · 2021Article
- Nucleotide exchange-dependent and nucleotide exchange-independent functions of plant heterotrimeric GTP-binding proteins.Science signaling · 2019Article
- G protein αq exerts expression level-dependent distinct signaling paradigms.Cellular signalling · 2019Article
- G-Protein Coupled Receptor Targeting on Myeloid Cells in Atherosclerosis.Frontiers in pharmacology · 2019Review
- Tissue-Specific Analysis of Pharmacological Pathways.CPT: pharmacometrics & systems pharmacology · 2018Article
- Potentiation of receptor responses induced by prolonged binding of GαFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Protein Interaction and Na/K-ATPase-Mediated Signal Transduction.Molecules (Basel, Switzerland) · 2017Review
- Predicting G protein-coupled receptor downstream signaling by tissue expression.Bioinformatics (Oxford, England) · 2016Article
- WNT Stimulation Dissociates a Frizzled 4 Inactive-State Complex with Gα12/13.Molecular pharmacology · 2016Article
5 more citing papers are in PubMed but not listed here.
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4 authors at 1 institution in 1 country.
Funding
Abstract
Heterotrimeric G proteins mediate physiological processes ranging from phototransduction to cell migration. In the accepted model of G protein signaling, Galphabetagamma heterotrimers physically dissociate after activation, liberating free Galpha subunits and Gbetagamma dimers. This model is supported by evidence obtained in vitro with purified proteins, but its relevance in vivo has been questioned. Here, we show that at least some heterotrimeric G protein isoforms physically dissociate after activation in living cells. Galpha subunits extended with a transmembrane (TM) domain and cyan fluorescent protein (CFP) were immobilized in the plasma membrane by biotinylation and cross-linking with avidin. Immobile CFP-TM-Galpha greatly decreased the lateral mobility of intracellular Gbeta1gamma2-YFP, indicating the formation of stable heterotrimers. A GTPase-deficient (constitutively active) mutant of CFP-TM-GalphaoA lost the ability to restrict Gbeta1gamma2-YFP mobility, whereas GTPase-deficient mutants of CFP-TM-Galphai3 and CFP-TM-Galphas retained this ability. Activation of cognate G protein-coupled receptors partially relieved the constraint on Gbeta1gamma2-YFP mobility induced by immobile CFP-TM-GalphaoA and CFP-TM-Galphai3 but had no effect on the constraint induced by CFP-TM-Galphas. These results demonstrate the physical dissociation of heterotrimers containing GalphaoA and Galphai3 subunits in living cells, supporting the subunit dissociation model of G protein signaling for these subunits. However, these results are also consistent with the suggestion that G protein heterotrimers (e.g., Galphas) may signal without physically dissociating.
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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.