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

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

2.1K
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...
2.1K
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

13.7K
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
13.7K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

2.3K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.3K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

6.6K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

79.4K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
79.4K
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

5.9K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.9K

You might also read

Related Articles

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

Sort by
Same author

Comparative efficacy of postoperative adjuvant chemoradiotherapy versus no chemoradiotherapy in the treatment of pancreatic adenocarcinoma.

BMC cancer·2026
Same author

Machine Learning Enabled Graph Analysis of Particulate Composites: Application to Solid-State Battery Cathodes.

ACS energy letters·2026
Same author

Functional drug screening of tumor organoids on an active-matrix digital microfluidic chip for cancer precision medicine.

Microsystems & nanoengineering·2026
Same author

Synergistic Mechanisms and Product Regulation in the Co-Pyrolysis of Biomass and Food Packaging Waste: A Study Based on Reaction Kinetics and GHG Calculation.

Foods (Basel, Switzerland)·2026
Same author

Radiation shielding performance of CeF<sub>3</sub>-Doped Li<sub>2</sub>O-PbO-GdF<sub>3</sub>-SiO<sub>2</sub> glasses: Monte Carlo simulation MCNPX and PHY-X/PSD study.

Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine·2026
Same author

Intraocular Lens Power Calculation for Combined Cataract and Pterygium Surgeries.

Clinical ophthalmology (Auckland, N.Z.)·2026

Related Experiment Video

Updated: Aug 22, 2025

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

8.7K

Multifaceted Roles of Retromer in EGFR Trafficking and Signaling Activation.

Zhe Yang1, Zhengyang Feng1, Zebin Li1

  • 1School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia.

Cells
|November 11, 2022
PubMed
Summary

The retromer complex, crucial for endosome trafficking, impacts epidermal growth factor receptor (EGFR) degradation. Its absence prolongs EGFR in early endosomes, affecting cell signaling and proliferation.

Keywords:
EGF receptorendosomesprotein traffickingretromer

More Related Videos

Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells
11:05

Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells

Published on: February 21, 2019

9.2K
Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
06:45

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay

Published on: May 26, 2011

15.3K

Related Experiment Videos

Last Updated: Aug 22, 2025

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

8.7K
Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells
11:05

Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells

Published on: February 21, 2019

9.2K
Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
06:45

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay

Published on: May 26, 2011

15.3K

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The retromer complex is vital for endosomal trafficking pathways.
  • Sorting nexins (SNXs) modulate retromer function and cargo specificity.
  • Endosomal trafficking of receptors like EGFR is critical for cellular signaling.

Purpose of the Study:

  • To investigate the role of the retromer complex, specifically Vps35, in epidermal growth factor receptor (EGFR) trafficking.
  • To dissect the contributions of individual retromer-SNX complexes to EGFR trafficking and downstream signaling.
  • To understand how retromer dysfunction impacts EGFR degradation and cellular responses.

Main Methods:

  • Utilized knockout (KO) cell line models to deplete retromer subunits (Vps35) and specific SNXs (SNX1/2, SNX3, SNX27).
  • Quantified EGFR protein levels and its association with cellular compartments (lysosomes, early endosomes).
  • Assessed EGFR degradation rates, AKT and ERK activation, and cell proliferation rates following EGF stimulation.

Main Results:

  • Vps35 depletion decreased EGFR protein levels in resting cells and enhanced EGFR association with lysosomes.
  • Vps35 KO cells showed reduced EGFR degradation, elevated AKT activation, and increased cell proliferation upon EGF stimulation.
  • Individual SNX knockouts (SNX1/2, SNX3, SNX27) promoted EGFR association with early endosomes, with distinct effects on degradation and AKT activation.

Conclusions:

  • Retromer complex, particularly Vps35, is essential for efficient EGFR trafficking and degradation from early endosomes.
  • Dysfunction in retromer-mediated trafficking leads to prolonged EGFR presence in early endosomes, impacting signaling pathways like AKT.
  • Specific SNXs contribute differentially to retromer-mediated EGFR trafficking, influencing degradation kinetics and cellular proliferation.