Ordered assembly of the ESCRT-III complex on endosomes is required to sequester cargo during MVB formation

Dev Cell. 2008 Oct;15(4):578-89. doi: 10.1016/j.devcel.2008.08.013.


The sequential action of the Vps27/HRS complex, ESCRT-I, -II, and -III is required to sort ubiquitinated transmembrane proteins to the lumen of lysosomes via the multivesicular body (MVB) pathway. While Vps27/HRS, ESCRT-I, and -II are recruited to endosomes as preformed complexes, the ESCRT-III subunits Vps20, Snf7, Vps24, and Vps2 only assemble into a complex on endosomes. We have addressed the pathway and the regulation for ESCRT-III assembly. Our findings indicate the ordered assembly of a transient 450 kDa ESCRT-III complex on endosomes. Despite biochemical and structural similarity, each subunit contributes a specific function. Vps20 nucleates transient oligomerization of Snf7, which appears to sequester MVB cargo. Vps24 terminates Snf7 oligomerization by recruiting Vps2, which subsequently engages the AAA-ATPase Vps4 to dissociate ESCRT-III. We propose that the ordered assembly and disassembly of ESCRT-III delineates an MVB sorting domain to sequester cargo and complete the last steps of MVB sorting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endosomal Sorting Complexes Required for Transport
  • Endosomes / chemistry
  • Endosomes / metabolism*
  • Fluorescence Resonance Energy Transfer
  • Green Fluorescent Proteins / metabolism
  • Lysosomes / metabolism
  • Molecular Weight
  • Nuclear Proteins / metabolism*
  • Protein Transport
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transport Vesicles / metabolism*
  • Vesicular Transport Proteins / chemistry
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*


  • Endosomal Sorting Complexes Required for Transport
  • Nuclear Proteins
  • SNF7 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • VPS27 protein, S cerevisiae
  • Vesicular Transport Proteins
  • Green Fluorescent Proteins