Multivesicular endosome biogenesis in the absence of ESCRTs

Traffic. 2009 Jul;10(7):925-37. doi: 10.1111/j.1600-0854.2009.00920.x. Epub 2009 Apr 10.


The endosomal sorting complex required for transport (ESCRT) protein machinery comprises four complexes, ESCRT-0, ESCRT-I, ESCRT-II and ESCRT-III, that facilitate receptor sorting into the lumen of multivesicular endosomes (MVEs) in order to terminate signalling receptors for final degradation within the lysosomes. Even though ESCRT proteins appear to be essential for the biogenesis of MVEs in Saccharomyces cerevisae, it is not clear whether ESCRT-independent pathways for MVE biogenesis exist in higher organisms. In this study we maximized inhibition of ESCRT-dependent pathway by depleting cells of key subunits of all four ESCRTs and followed MVE formation and epidermal growth factor (EGF) receptor (EGFR) traffic using electron and confocal microscopy. There was a dramatic alteration in the morphology of components of the endocytic pathway in ESCRT-depleted cells, but early and late endosomes stayed clearly differentiated. Importantly, although EGF-induced formation of MVEs was highly sensitive to ESCRT depletion, EGF-independent formation of MVEs could still occur. The MVEs remaining in ESCRT-depleted cells contained enlarged intralumenal vesicles into which EGFRs were not sorted. Our observations suggest that both ESCRT-dependent and ESCRT-independent mechanisms of MVE biogenesis exist in mammalian cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Biomarkers / metabolism
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Endosomal Sorting Complexes Required for Transport
  • Endosomes / metabolism*
  • Endosomes / ultrastructure
  • Humans
  • Immunohistochemistry
  • Microscopy, Immunoelectron
  • Multiprotein Complexes / metabolism*
  • Platelet Membrane Glycoproteins / metabolism
  • Protein Subunits / genetics
  • Protein Subunits / metabolism*
  • Proteins / genetics
  • Proteins / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Tetraspanin 30
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*


  • Antigens, CD
  • Biomarkers
  • CD63 protein, human
  • CHMP3 protein, human
  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Multiprotein Complexes
  • Platelet Membrane Glycoproteins
  • Protein Subunits
  • Proteins
  • RNA, Small Interfering
  • SNF8 protein, human
  • Saccharomyces cerevisiae Proteins
  • Tetraspanin 30
  • Transcription Factors
  • Tsg101 protein
  • Vesicular Transport Proteins