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Multivesicular endosome biogenesis in the absence of ESCRTs

Susanne Stuffers1, Catherine Sem Wegner, Harald Stenmark

  • 1Department of Biochemistry, Institute for Cancer Research, The Norwegian Radiumhospital and Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, N-0310 Oslo, Norway.

Traffic (Copenhagen, Denmark)
|June 4, 2009
PubMed

Insights

Mammalian cells utilize both ESCRT-dependent and ESCRT-independent pathways for multivesicular endosome (MVE) biogenesis. Even when ESCRT proteins are depleted, MVEs form, though EGFR sorting is impaired.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Endosomal Sorting

Background:

  • The endosomal sorting complex required for transport (ESCRT) machinery is crucial for multivesicular endosome (MVE) biogenesis and receptor degradation.
  • The existence of ESCRT-independent pathways for MVE formation in higher organisms remains unclear.

Purpose of the Study:

  • To investigate the existence of ESCRT-independent pathways for MVE biogenesis in mammalian cells.
  • To analyze the impact of ESCRT depletion on MVE formation and epidermal growth factor receptor (EGFR) trafficking.

Main Methods:

  • Depletion of key ESCRT subunits (ESCRT-0, -I, -II, -III) in mammalian cells.
  • Utilized electron microscopy and confocal microscopy to observe MVE formation and EGFR traffic.
  • Assessed endosomal pathway morphology and EGFR sorting into MVEs.

Main Results:

  • ESCRT depletion significantly altered endocytic pathway morphology but maintained endosome differentiation.
  • EGF-induced MVE formation was sensitive to ESCRT depletion, yet EGF-independent MVE formation persisted.
  • MVEs in ESCRT-depleted cells exhibited enlarged intralumenal vesicles and failed EGFR sorting.

Conclusions:

  • Mammalian cells possess both ESCRT-dependent and ESCRT-independent mechanisms for MVE biogenesis.
  • ESCRT proteins are essential for efficient EGFR sorting into MVEs, but not solely for MVE formation.

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