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Related Concept Videos

Maturation of Endosomes01:28

Maturation of Endosomes

The early endosome containing internalized molecules matures through transformations in its location, morphology, intraluminal pH, and membrane protein composition. Together, these changes result in a more acidic late endosome that contains multiple intraluminal vesicles; therefore, the late endosome is also called a multivesicular body (MVB).
Changes in location
The maturing endosome moves along microtubules from the periphery of the cell towards the perinuclear region. This movement of the...
Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
The Early Endosome: Endocytosis of Transferrin01:28

The Early Endosome: Endocytosis of Transferrin

Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
ER Retrieval Pathway01:45

ER Retrieval Pathway

In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
Clathrin Coated Vesicles01:12

Clathrin Coated Vesicles

Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...

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Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins
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Cullin-3 regulates late endosome maturation.

Jatta Huotari1, Nathalie Meyer-Schaller, Michaela Hubner

  • 1Institute of Biochemistry, Department of Biology, ETH Zurich, CH-8093 Zurich, Switzerland.

Proceedings of the National Academy of Sciences of the United States of America
|January 6, 2012
PubMed
Summary

Cullin-3 (Cul3) is essential for late endosome maturation and the proper trafficking of viral and cellular cargoes. Depleting Cul3 causes endosomal defects, trapping viruses and delaying receptor degradation.

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Published on: December 13, 2013

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Virology

Background:

  • Cullin-3 (Cul3) is a scaffolding protein within the BTB-Cul3-Rbx1 ubiquitin E3 ligase complex.
  • The precise functions of Cul3 complexes in endosomal trafficking remain incompletely understood.

Purpose of the Study:

  • To investigate the role of Cul3 in the endolysosomal pathway.
  • To determine the impact of Cul3 depletion on the trafficking of specific endosomal cargoes.

Main Methods:

  • RNA interference (RNAi) was used to deplete Cul3 expression.
  • Trafficking of influenza A virus (IAV) and epidermal growth factor receptor (EGFR) was analyzed.
  • Morphological analysis of late endosomes was performed using markers like Rab7.

Main Results:

  • Cul3 depletion led to trafficking defects in both IAV and EGFR.
  • IAV was trapped in late endosomes, with impaired capsid uncoating.
  • EGFR degradation was delayed, and EGF accumulated in late endosomes/lysosomes.
  • Cul3-depleted cells exhibited enlarged, vacuolated late endosomes.

Conclusions:

  • Cul3 plays a critical role in regulating late endosome maturation.
  • Cul3 is essential for the efficient trafficking and processing of endosomal cargoes, including viral particles and receptors.