Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes

Annu Rev Cell Dev Biol. 2018 Oct 6;34:85-109. doi: 10.1146/annurev-cellbio-100616-060600. Epub 2018 Aug 10.

Abstract

The endosomal sorting complexes required for transport (ESCRT) pathway mediates cellular membrane remodeling and fission reactions. The pathway comprises five core complexes: ALIX, ESCRT-I, ESCRT-II, ESCRT-III, and Vps4. These soluble complexes are typically recruited to target membranes by site-specific adaptors that bind one or both of the early-acting ESCRT factors: ALIX and ESCRT-I/ESCRT-II. These factors, in turn, nucleate assembly of ESCRT-III subunits into membrane-bound filaments that recruit the AAA ATPase Vps4. Together, ESCRT-III filaments and Vps4 remodel and sever membranes. Here, we review recent advances in our understanding of the structures, activities, and mechanisms of the ESCRT-III and Vps4 machinery, including the first high-resolution structures of ESCRT-III filaments, the assembled Vps4 enzyme in complex with an ESCRT-III substrate, the discovery that ESCRT-III/Vps4 complexes can promote both inside-out and outside-in membrane fission reactions, and emerging mechanistic models for ESCRT-mediated membrane fission.

Keywords: AAA ATPase; ESCRT pathway; ESCRT-III; Vps4; membrane fission; membrane remodeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Actin Cytoskeleton / chemistry
  • Actin Cytoskeleton / genetics*
  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / genetics*
  • Cell Membrane / chemistry
  • Cell Membrane / genetics*
  • Cytokinesis
  • Endosomal Sorting Complexes Required for Transport / chemistry
  • Endosomal Sorting Complexes Required for Transport / genetics*
  • Endosomes / chemistry
  • Endosomes / genetics
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics*

Substances

  • Endosomal Sorting Complexes Required for Transport
  • Multiprotein Complexes
  • Saccharomyces cerevisiae Proteins
  • VPS4 protein, S cerevisiae
  • Adenosine Triphosphatases