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

Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

19.0K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
19.0K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

8.0K
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...
8.0K
GPCR Desensitization01:12

GPCR Desensitization

8.5K
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...
8.5K
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

12.1K
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...
12.1K
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

133.4K
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.
133.4K
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

6.5K
6.5K

You might also read

Related Articles

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

Sort by
Same author

ADHD and metabolic syndrome: behavioral and weight-related pathways to cardiovascular risk.

European archives of psychiatry and clinical neuroscience·2026
Same author

[Is it all bipolar? Differential diagnosis of mood swings in young adulthood].

Der Nervenarzt·2026
Same author

Selective octopaminergic tuning of mushroom body circuits during memory formation.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

Structural basis of GAIN domain autoproteolysis and cleavage-resistance in the adhesion G-protein coupled receptors.

Nature communications·2026
Same author

Adhesion G protein-coupled receptors.

Pharmacological reviews·2026
Same author

The elephant in the adhesion GPCR room.

Science signaling·2026
Same journal

Endothelial Cell Phenotypic Plasticity in Atherosclerosis.

Handbook of experimental pharmacology·2026
Same journal

Endothelial Dysfunction and Neurovascular Alterations in Autism Spectrum Disorder.

Handbook of experimental pharmacology·2026
Same journal

Molecular Mechanisms of Endothelial Shear Stress Mechanotransduction in Health and Disease.

Handbook of experimental pharmacology·2026
Same journal

Microvasculature of the Pancreatic Islets of Langerhans in Health and Diabetes.

Handbook of experimental pharmacology·2026
Same journal

Mechanisms of Actions of Physiological, Pharmacological, and Toxicological Dietary Bioactive Inorganic Boron.

Handbook of experimental pharmacology·2026
Same journal

BNCT Plus Luminescence: New Paradigm for Boron-Containing Drug Design.

Handbook of experimental pharmacology·2026
See all related articles

Related Experiment Video

Updated: Mar 12, 2026

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

1.0K

Control of Adhesion GPCR Function Through Proteolytic Processing.

Matthias Nieberler1, Robert J Kittel1, Alexander G Petrenko2

  • 1Department of Neurophysiology, Institute of Physiology, University of Würzburg, Röntgenring 9, Würzburg, 97070, Germany.

Handbook of Experimental Pharmacology
|November 11, 2016
PubMed
Summary
This summary is machine-generated.

Adhesion G protein-coupled receptors (aGPCRs) undergo unique proteolytic processing, primarily via the GAIN domain, influencing their function and signaling. This review details these cleavage events and their impact on aGPCRs.

Keywords:
Adhesion GPCRAutoproteolysisGAIN domainGPSProteolysis

More Related Videos

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
10:13

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding

Published on: June 9, 2017

17.4K
A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4
06:56

A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4

Published on: March 10, 2018

14.6K

Related Experiment Videos

Last Updated: Mar 12, 2026

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

1.0K
Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
10:13

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding

Published on: June 9, 2017

17.4K
A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4
06:56

A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4

Published on: March 10, 2018

14.6K

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Adhesion G protein-coupled receptors (aGPCRs) exhibit unusual proteolytic processing.
  • The GPCR autoproteolysis-inducing (GAIN) domain is central to aGPCR autoproteolysis.
  • Proteolytic events are critical for aGPCR function, signaling, and cellular effects.

Purpose of the Study:

  • To review current knowledge on GAIN domain-mediated and independent aGPCR cleavage.
  • To elucidate the significance of these cleavage events for aGPCR pharmacology and cell biology.
  • To compare aGPCR proteolysis with other proteolysis-governed signaling pathways.

Main Methods:

  • Literature review and synthesis of existing research on aGPCR proteolytic processing.
  • Analysis of biochemical and functional studies on GAIN domain activity.
  • Comparative analysis with proteolysis-dependent signaling pathways like Notch and ephrin.

Main Results:

  • All aGPCRs possess the GAIN domain, which mediates autoproteolysis in many homologs.
  • Additional proteolytic steps can occur, including ectodomain shedding for independent function.
  • Proteolytic processing significantly impacts aGPCR signaling and cellular behavior.

Conclusions:

  • Proteolytic processing is a key regulatory mechanism for aGPCRs.
  • Understanding aGPCR cleavage is crucial for their pharmacological targeting and comprehending their biological roles.
  • aGPCR proteolysis offers insights into broader cell signaling mechanisms involving proteolysis.