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

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 the...
Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

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 cells.
Two...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

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 produces two-second...

You might also read

Related Articles

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

Sort by
Same author

Leveraging human genetic variation to therapeutically target hundreds of genes with dominant & dispensable disease alleles.

medRxiv : the preprint server for health sciences·2026
Same author

Using image classifiers to predict CMT2A disease-relevant mitochondrial motility phenotypes in iPSC motor neurons.

bioRxiv : the preprint server for biology·2026
Same author

Monitoring biological effects of somatic cell genome editing.

Nature reviews. Genetics·2026
Same author

Generation of WTD, a control human iPSC line for genetic research.

Stem cell research·2025
Same author

Haplotype editing with CRISPR-Cas9 as a therapeutic approach for dominant-negative missense mutations in NEFL.

Molecular therapy : the journal of the American Society of Gene Therapy·2025
Same author

Characterizing and controlling CRISPR repair outcomes in nondividing human cells.

Nature communications·2025
Same journal

Efficient evidence-based genome annotation with EviAnn.

Nature methods·2026
Same journal

ClairS: a deep-learning method for long-read tumor-normal pair somatic small variant calling.

Nature methods·2026
Same journal

RNAbpFlow: base pair-augmented SE(3) flow matching for conditional RNA 3D structure generation.

Nature methods·2026
Same journal

Spatio-DARLIN enables robust and efficient in situ lineage tracing in mice at single-cell resolution.

Nature methods·2026
Same journal

EasyGrid: a versatile platform for automated cryo-EM sample preparation and quality control.

Nature methods·2026
Same journal

Cloud-based microscope enables live neuroimaging for 24 h and beyond with worldwide access.

Nature methods·2026
See all related articles

Related Experiment Video

Updated: Jul 3, 2026

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

Engineering GPCR signaling pathways with RASSLs.

Bruce R Conklin1, Edward C Hsiao, Sylvie Claeysen

  • 1Gladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, California 94158, USA. bconklin@gladstone.ucsf.edu

Nature Methods
|August 1, 2008
PubMed
Summary
This summary is machine-generated.

Researchers engineered receptors activated solely by synthetic ligands (RASSLs) for precise control over cellular signaling. These designer G protein-coupled receptors (GPCRs) offer new tools for in vivo studies.

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

Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
09:40

Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum

Published on: September 20, 2011

Related Experiment Videos

Last Updated: Jul 3, 2026

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

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

Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
09:40

Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum

Published on: September 20, 2011

Area of Science:

  • Molecular Biology
  • Pharmacology
  • Biochemistry

Background:

  • G protein-coupled receptors (GPCRs) are crucial cell surface receptors involved in numerous physiological processes.
  • Controlling GPCR signaling with high specificity and temporal precision in vivo remains a significant challenge.
  • Existing methods often lack the necessary precision or are influenced by endogenous signaling molecules.

Purpose of the Study:

  • To introduce and review engineered receptors activated solely by synthetic ligands (RASSLs).
  • To highlight the development of RASSLs for precise spatiotemporal control of GPCR signaling pathways.
  • To facilitate the adoption and application of RASSLs in biological research.

Main Methods:

  • Design and engineering of novel G protein-coupled receptors (GPCRs).
  • Modification of GPCRs to be unresponsive to endogenous ligands.
  • Development of synthetic small molecules for targeted RASSL activation at nanomolar concentrations.
  • Validation of RASSLs across major GPCR signaling pathways (G(s), G(i), and G(q)).

Main Results:

  • Successful creation of designer GPCRs (RASSLs) activated exclusively by synthetic ligands.
  • Demonstrated precise spatiotemporal control over GPCR signaling in vivo using RASSLs.
  • Established RASSLs for all three major GPCR signaling pathways, expanding their utility.
  • RASSLs exhibit high sensitivity, activated by nanomolar concentrations of inert small molecules.

Conclusions:

  • RASSLs represent a powerful and versatile tool for precise manipulation of GPCR signaling.
  • These engineered receptors overcome limitations of endogenous ligands, enabling new research avenues.
  • The availability of RASSLs across major pathways significantly advances in vivo pharmacology and cell biology studies.