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Related Concept Videos

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Intralumenal Vesicles and Multivesicular Bodies

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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...
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The Early Endosome: Endocytosis of Transferrin01:28

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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...
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Overview of Protein Sorting and Transport01:45

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Eukaryotic cells have different membrane-bound organelles with distinct protein requirements. The process by which proteins are targeted to a specific organelle is called protein sorting.
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ER Retrieval Pathway01:45

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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.
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Recycling Endosomes and Transcytosis00:58

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The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
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After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
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Related Experiment Video

Updated: May 4, 2026

Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells
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Ubiquitin-dependent sorting in endocytosis.

Robert C Piper1, Ivan Dikic, Gergely L Lukacs

  • 1Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242.

Cold Spring Harbor Perspectives in Biology
|January 4, 2014
PubMed
Summary

Ubiquitin (Ub) targets plasma membrane proteins for lysosomal degradation. This process involves Ub-binding complexes that recognize Ub signals during endocytosis and sorting into multivesicular bodies.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Protein Degradation

Background:

  • Ubiquitin (Ub) modification is crucial for protein trafficking and degradation.
  • Membrane proteins at the plasma membrane are targeted for lysosomal degradation via ubiquitination.
  • Ubiquitin acts as a key sorting signal in the endocytic pathway.

Purpose of the Study:

  • To provide an overview of how membrane proteins are ubiquitinated and deubiquitinated.
  • To explain how the ubiquitin signal is interpreted by endocytic sorting machineries.
  • To highlight the role of ubiquitin-binding domains in protein sorting.

Main Methods:

  • Literature review of ubiquitination and deubiquitination processes.
  • Analysis of ubiquitin recognition by protein complexes.

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  • Examination of ubiquitin-binding domains in sorting machinery.
  • Main Results:

    • Ubiquitin targets membrane proteins for internalization and sorting into multivesicular late endosomes.
    • Ubiquitin-binding domains on sorting complexes mediate recognition of ubiquitinated proteins.
    • Ubiquitination of sorting complexes themselves offers regulatory mechanisms.

    Conclusions:

    • Ubiquitin is a central signal for directing membrane proteins to lysosomes for degradation.
    • The endocytic pathway utilizes specific machineries to interpret ubiquitin signals.
    • Regulation of ubiquitination and deubiquitination is critical for protein homeostasis.