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Related Experiment Videos

Protein sorting into multivesicular endosomes.

Camilla Raiborg1, Tor Erik Rusten, Harald Stenmark

  • 1Department of Biochemistry, Institute for Cancer Research, the Norwegian Radium Hospital, Montebello, N-0310, Oslo, Norway.

Current Opinion in Cell Biology
|August 2, 2003
PubMed
Summary
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Monoubiquitination targets proteins for sorting into multivesicular endosomes, a key step in receptor downregulation and lysosome formation. The ESCRT machinery, including Hrs/Vps27, drives this process and is hijacked by viruses like HIV.

Area of Science:

  • Cell biology
  • Molecular mechanisms of endosomal sorting
  • Viral pathogenesis

Background:

  • Multivesicular endosomes (MVEs) are crucial for receptor downregulation and secretory lysosome biogenesis.
  • Understanding protein sorting into MVEs is vital for cellular homeostasis and disease research.
  • Past research has begun elucidating the machinery governing MVE formation and cargo selection.

Purpose of the Study:

  • To investigate the molecular mechanisms of protein sorting into MVEs.
  • To identify the key protein complexes involved in MVE formation.
  • To explore how viruses like HIV interact with MVE pathways.

Main Methods:

  • Analysis of monoubiquitination as a sorting signal.
  • Characterization of the ubiquitin-binding protein Hrs/Vps27.

Related Experiment Videos

  • Investigation of the ESCRT-I, -II, and -III complexes in MVE biogenesis.
  • Studying the role of MVE machinery in viral budding.

    • Main Results:

    • Monoubiquitination serves as a signal for sorting transmembrane proteins into intraluminal vesicles (ILVs) of MVEs.
    • The Hrs/Vps27 protein complex is central to this ubiquitin-dependent sorting pathway.
    • The ESCRT-I, -II, and -III complexes are essential for both protein sorting into ILVs and MVE formation.
    • Enveloped viruses, such as HIV, can hijack the ESCRT machinery for their own budding from the plasma membrane.

    Conclusions:

    • The study clarifies the molecular basis of protein sorting into MVEs, highlighting monoubiquitination and the ESCRT pathway.
    • This fundamental cellular process is co-opted by viruses, demonstrating a link between endosomal trafficking and viral replication.
    • Findings provide insights into receptor downregulation, lysosome biogenesis, and viral pathogenesis.