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

Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

2.3K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.3K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.0K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

8.6K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.6K
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

3.1K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.1K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

5.1K
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...
5.1K
GPCR Desensitization01:12

GPCR Desensitization

5.7K
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...
5.7K

You might also read

Related Articles

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

Sort by
Same author

Sphingosine‑1‑phosphate receptor 1 enhances olfactory receptor 51E1‑mediated inhibition of proliferation via Src/JNK signaling in prostate cancer cells.

Oncology reports·2026
Same author

Age-related increase of NLRC4 inflammasome and TGF-β1 signaling exacerbates airway inflammation and remodeling in asthma.

GeroScience·2026
Same author

MCC950 Suppresses Hepatic Inflammaging by Inhibiting NLRP3 Inflammasome Activation in Spontaneously Aged Mice.

Frontiers in bioscience (Landmark edition)·2026
Same author

Effects of composition, finishing, and salivary pH on physicomechanical and biological properties of additively manufactured resin-ceramic composites: An in vitro study.

Journal of dentistry·2026
Same author

Activation of the pituitary adenylate cyclase-activating polypeptide type I receptor promotes neuroblastoma proliferation and migration through distinct G protein pathways.

Cell communication and signaling : CCS·2026
Same author

Design, Synthesis, and Biological Evaluation of C2-(N-Substituted Amino) Truncated 4'-Thioadenosine Derivatives as A<sub>2A</sub>AR and A<sub>3</sub>AR Dual Ligands.

ACS medicinal chemistry letters·2025

Related Experiment Video

Updated: May 25, 2025

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

13.6K

Regulation of CXCR4 function by S1P1 through heteromerization.

Hyun-Tae Kim1, Jae-Yeon Jeong2, Won-Ki Huh3,4,5

  • 1School of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea.

Cell Communication and Signaling : CCS
|February 26, 2025
PubMed
Summary
This summary is machine-generated.

This study reveals that sphingosine-1-phosphate receptor type 1 (S1P1) forms complexes with C-X-C chemokine receptor type 4 (CXCR4), uniquely modulating CXCR4 signaling. These CXCR4-S1P1 heteromers impact immune cell trafficking by altering receptor function.

Keywords:
CXCR4G protein-coupled receptorHeteromerS1P1

More Related Videos

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

8.8K
Retroviral Overexpression of CXCR4 on Murine B-1a Cells and Adoptive Transfer for Targeted B-1a Cell Migration to the Bone Marrow and IgM Production
08:22

Retroviral Overexpression of CXCR4 on Murine B-1a Cells and Adoptive Transfer for Targeted B-1a Cell Migration to the Bone Marrow and IgM Production

Published on: May 31, 2020

5.0K

Related Experiment Videos

Last Updated: May 25, 2025

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

13.6K
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

8.8K
Retroviral Overexpression of CXCR4 on Murine B-1a Cells and Adoptive Transfer for Targeted B-1a Cell Migration to the Bone Marrow and IgM Production
08:22

Retroviral Overexpression of CXCR4 on Murine B-1a Cells and Adoptive Transfer for Targeted B-1a Cell Migration to the Bone Marrow and IgM Production

Published on: May 31, 2020

5.0K

Area of Science:

  • Immunology
  • Cellular Biology
  • Biochemistry

Background:

  • Immune cell trafficking relies on CXCL12/CXCR4 and S1P/S1P1 gradients.
  • S1P1 counteracts CXCR4 retention signals, facilitating immune cell egress.
  • Molecular mechanisms of CXCR4-S1P1 interplay were previously unclear.

Purpose of the Study:

  • To investigate CXCR4-S1P1 heteromerization.
  • To elucidate the functional consequences of this heteromerization on signaling pathways.
  • To understand the role of these heteromers in immune cell migration.

Main Methods:

  • Detected CXCR4-S1P1 heteromerization using BiFC, PLA, and BRET assays.
  • Assessed functional properties via cAMP assays, G protein activation, β-arrestin recruitment, ligand binding, calcium mobilization, and transwell migration.
  • Utilized CRISPR/Cas9 and lentiviral transduction to generate cells with specific receptor deficiencies or overexpression.

Main Results:

  • Confirmed CXCR4-S1P1 heteromerization in cells overexpressing both receptors.
  • Demonstrated unidirectional modulation: S1P1 interferes with CXCR4 signaling, but not vice versa.
  • Identified disruption of CXCR4-Gαi pre-association and oligomerization by S1P1 as key mechanisms, with S1P1's transmembrane domain 3 being crucial.
  • Observed diminished CXCR4-mediated signaling and migration in S1P1-overexpressing cells and enhanced functions in S1P1-deficient cells.

Conclusions:

  • Identified functional CXCR4-S1P1 heteromers.
  • Established unidirectional modulation of CXCR4 by S1P1 through disruption of G protein pre-association and oligomerization.
  • Highlighted the regulatory role of the S1P/S1P1 axis in CXCR4 signaling within heteromers, offering insights into immune cell trafficking.