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Related Concept Videos

GPCR Desensitization01:12

GPCR Desensitization

6.0K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
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G Protein-coupled Receptors01:15

G Protein-coupled Receptors

11.9K
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...
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IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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G-protein Coupled Receptors01:21

G-protein Coupled Receptors

118.6K
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.
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Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

2.0K
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,...
2.0K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

5.5K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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Related Experiment Video

Updated: Jun 28, 2025

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

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Beneath the surface: endosomal GPCR signaling.

Emmanuel Flores-Espinoza1, Alex R B Thomsen1

  • 1Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA; NYU Pain Research Center, New York University College of Dentistry, New York, NY 10010, USA.

Trends in Biochemical Sciences
|April 20, 2024
PubMed
Summary

G protein-coupled receptors (GPCRs) signal from inside cells after internalization, challenging traditional views. This endosomal signaling offers new therapeutic targets for various diseases.

Keywords:
GPCR: G protein, β-arrestindesensitizationendosomal signalingmegaplexes

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Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
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Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
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Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
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Area of Science:

  • Cellular Biology
  • Molecular Pharmacology
  • Signal Transduction

Background:

  • G protein-coupled receptors (GPCRs) traditionally signal from the cell surface.
  • Desensitization and internalization mediated by β-arrestin (βarr) were thought to terminate signaling.

Purpose of the Study:

  • To review the mechanistic basis of endosomal GPCR signaling.
  • To discuss the physiological implications and therapeutic potential of this signaling pathway.

Main Methods:

  • Literature review of recent findings on GPCR signaling.
  • Analysis of mechanistic studies on endosomal receptor activity.

Main Results:

  • GPCRs can continue activating G proteins after internalization into endosomes.
  • βarr-mediated events do not always terminate GPCR signaling.

Conclusions:

  • Endosomal GPCR signaling represents a newly appreciated mode of cellular communication.
  • Targeting this pathway offers novel pharmacological strategies.