Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

G Protein-coupled Receptors01:15

G Protein-coupled Receptors

15.6K
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...
15.6K
Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

3.5K
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,...
3.5K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

6.7K
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...
6.7K
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

130.4K
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.
130.4K
GPCR Desensitization01:12

GPCR Desensitization

7.6K
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...
7.6K
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

9.9K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
9.9K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Pancreatic islet α cell function and proliferation require the arginine transporter SLC7A2.

The Journal of clinical investigation·2026
Same author

Extracellular domain-dependent modulation of class B1 G-protein-coupled receptor signaling.

Molecular pharmacology·2026
Same author

In vivo functional profiling and structural characterization of the human <i>GLP1R</i> A316T variant.

Science advances·2026
Same author

GLP-1R biased cAMP agonism maintains glycemic control with reduced malaise and emesis in preclinical mammalian models.

Diabetes, obesity & metabolism·2026
Same author

Long-acting GIPR agonist LY3537021 reduces body weight and fasting blood glucose in patients with T2D: Preclinical development and phase 1 randomized ascending dose studies.

Molecular metabolism·2025
Same author

Spatially diffuse cAMP signalling with oppositely biased GLP-1 receptor agonists in β-cells despite differences in receptor localisation.

Molecular metabolism·2025

Related Experiment Video

Updated: Dec 11, 2025

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

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

Published on: February 20, 2018

9.3K

Synthetic protease-activated class B GPCRs.

Francis S Willard1, Tamika D Meredith1, Aaron D Showalter2

  • 1Quantitative Biology, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.

Biochemical and Biophysical Research Communications
|August 24, 2020
PubMed
Summary

Researchers created novel G-protein coupled receptor (GPCR) fusion proteins activated by enzymes. This system enables studying structure-function relationships of peptide-binding GPCRs and their signaling pathways.

Keywords:
Class BEnterokinaseG-protein coupled receptorGlucagon-like peptide-1 receptorSynthetic biology

More Related Videos

Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control
07:13

Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control

Published on: May 24, 2024

807
Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors
16:16

Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors

Published on: September 13, 2013

15.6K

Related Experiment Videos

Last Updated: Dec 11, 2025

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

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

Published on: February 20, 2018

9.3K
Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control
07:13

Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control

Published on: May 24, 2024

807
Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors
16:16

Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors

Published on: September 13, 2013

15.6K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • G-protein coupled receptors (GPCRs) are crucial for cellular communication in multicellular organisms.
  • Understanding GPCR structure-function is vital for drug discovery and basic research.
  • Class B GPCRs, like the glucagon-like peptide-1 receptor (GLP-1R), present unique challenges for structure-function studies.

Purpose of the Study:

  • To develop a novel method for probing the structure-function relationships of class B GPCRs.
  • To create and validate receptor-ligand fusion proteins activated by exogenous enzymes.
  • To investigate the potential of this system in studying GLP-1R signaling and insulin secretion.

Main Methods:

  • Generation of fusion proteins combining the GLP-1R with GLP-1 and exendin-4 peptides, featuring enterokinase-cleavable N-termini.
  • Activation of fusion proteins via enterokinase to release active N-termini, mimicking natural ligands.
  • Measurement of cAMP accumulation in response to enterokinase-activated GLP-1R fusion proteins.
  • Assessment of glucose-dependent insulin secretion in insulinoma cells using the developed system.

Main Results:

  • Successful generation of GLP-1R-ligand fusion proteins activated by enterokinase.
  • Demonstration of enterokinase-dependent GLP-1R-mediated cAMP accumulation.
  • Identification of structure-activity relationships concerning linker length and peptide sequence.
  • Validation of the system in a physiological context, showing induced insulin secretion in insulinoma cells.

Conclusions:

  • The developed receptor-ligand fusion protein system provides a novel strategy for studying peptide-binding GPCRs.
  • This approach allows for enzyme-inducible activation, facilitating structure-function analysis.
  • The system is applicable to physiologically relevant models, offering new avenues for GPCR research and therapeutic development.