Related Experiment Video
Updated: Jun 7, 2026
09:40
Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
Published on: September 20, 2011
Variability in G-protein-coupled signaling studied with microfluidic devices
Xiaoyan Robert Bao1, Iain D C Fraser, Estelle A Wall
1Department of Applied Physics, California Institute of Technology, Pasadena, USA. bao@chgr.mgh.harvard.edu
Biophysical Journal
|October 21, 2010
Summary
Cellular responses vary due to long-lived differences between cells, not random signaling. This study quantifies variability in G-protein-activated calcium release and purinergic receptor signaling in macrophages.
Area of Science:
- Cellular Biology
- Biophysics
- Immunology
Background:
- Cellular responses to identical stimuli exhibit variability, even among genetically identical cells.
- The origins of this cell-to-cell variability in biological responses remain largely unknown.
- Understanding response variability is crucial for accurate modeling of cellular dynamics.
Purpose of the Study:
- To investigate the sources of variability in G-protein-activated calcium release in individual macrophages.
- To determine the contribution of receptor-specific factors to cellular response variability.
- To characterize the saturation properties of signaling pathways downstream of purinergic receptors.
Main Methods:
- Development of a microfluidic system for tracking individual cell responses across multiple stimulations.
- Quantitative analysis of calcium release dynamics in RAW264.7 macrophages.
- Investigation of responses mediated by P2Y family purine receptors, specifically P2Y6.
Main Results:
- Amplitude variations in G-protein-activated calcium release are primarily extrinsic, stemming from stable cell-specific differences.
- Approximately one-third of the variability in calcium release linked to P2Y receptors is receptor-specific.
- The signaling pathway downstream of P2Y6 receptor activation exhibits moderate saturation.
Conclusions:
- Cellular variability in G-protein-coupled calcium signaling is largely driven by persistent, cell-intrinsic factors.
- Purinergic receptor signaling contributes significantly to cell-specific response variability.
- These findings provide critical data for developing and refining single-cell models of calcium dynamics.
Related Concept Videos
01:21G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
01:21G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
01:30Transducer Mechanism: G Protein–Coupled Receptors
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...
01:15G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
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...
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...
01:15G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
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...
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...
02:14GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...