Related Experiment Video
Updated: Apr 18, 2026

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
Published on: June 9, 2017
Nuclear G protein signaling: new tricks for old dogs
Rhiannon Campden1, Nicolas Audet, Terence E Hébert
1Department of Pharmacology and Therapeutics, McGill University, Montréal, Canada.
Abstract:
According to the standard model of G protein-coupled receptor (GPCR) signaling, GPCRs are localized to the cell membrane where they respond to extracellular signals. Stimulation of GPCRs leads to the activation of heterotrimeric G proteins and their intracellular signaling pathways. However, this model fails to accommodate GPCRs, G proteins, and their downstream effectors that are found on the nuclear membrane or in the nucleus. Evidence from isolated nuclei indicates the presence of GPCRs on the nuclear membrane that can activate similar G protein-dependent signaling pathways in the nucleus as at the cell surface. These pathways also include activation of cyclic adenosine monophosphate, calcium and nitric oxide synthase signaling in cardiomyocytes. In addition, a number of distinct heterotrimeric and monomeric G proteins have been found in the nucleus of various cell types. This review will focus on understanding the function of nuclear G proteins with a focus on cardiac signaling where applicable.
Insights
G protein-coupled receptors (GPCRs) and G proteins function within the nucleus, not just the cell membrane. Nuclear signaling pathways impact cellular functions, including in heart cells.
Area of Science:
- Cell Biology
- Molecular Biology
- Cardiology
Background:
- The standard model places G protein-coupled receptors (GPCRs) exclusively on the cell membrane.
- This model does not account for GPCRs, G proteins, and signaling molecules found within the nucleus.
- Emerging evidence highlights nuclear localization and function of these signaling components.
Purpose of the Study:
- To review the presence and function of G proteins within the nucleus.
- To explore nuclear G protein-dependent signaling pathways.
- To emphasize cardiac signaling implications of nuclear G proteins.
Main Methods:
- Review of existing literature on nuclear GPCRs and G proteins.
- Analysis of evidence from isolated nuclei studies.
- Focus on G protein signaling pathways in cardiomyocytes.
Main Results:
- GPCRs are present on the nuclear membrane and can activate G protein signaling pathways within the nucleus.
- Nuclear G protein pathways can mimic cell surface signaling, including cyclic adenosine monophosphate, calcium, and nitric oxide synthase activation.
- Various heterotrimeric and monomeric G proteins are identified in the nucleus across different cell types.
Conclusions:
- The function of GPCRs and G proteins extends beyond the cell membrane to the nucleus.
- Nuclear G protein signaling plays a role in cellular processes, particularly evident in cardiac cells.
- Further research into nuclear G protein function is warranted.
More Related Videos
07:41A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
09:40Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
Published on: September 20, 2011
Related Concept Videos
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
G Protein-coupled Receptors
G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Amplifying Signals via Second Messengers
G-protein Coupled Receptors
G-protein Coupled Receptors