ATP-dependent force generation and membrane scission by ESCRT-III and Vps4

Science. 2018 Dec 21;362(6421):1423-1428. doi: 10.1126/science.aat1839.


The endosomal sorting complexes required for transport (ESCRTs) catalyze reverse-topology scission from the inner face of membrane necks in HIV budding, multivesicular endosome biogenesis, cytokinesis, and other pathways. We encapsulated ESCRT-III subunits Snf7, Vps24, and Vps2 and the AAA+ ATPase (adenosine triphosphatase) Vps4 in giant vesicles from which membrane nanotubes reflecting the correct topology of scission could be pulled. Upon ATP release by photo-uncaging, this system generated forces within the nanotubes that led to membrane scission in a manner dependent upon Vps4 catalytic activity and Vps4 coupling to the ESCRT-III proteins. Imaging of scission revealed Snf7 and Vps4 puncta within nanotubes whose presence followed ATP release, correlated with force generation and nanotube constriction, and preceded scission. These observations directly verify long-standing predictions that ATP-hydrolyzing assemblies of ESCRT-III and Vps4 sever membranes.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / metabolism*
  • Adenosine Triphosphate / metabolism*
  • Biocatalysis
  • Cell Membrane / metabolism*
  • Cell Membrane / ultrastructure
  • Endosomal Sorting Complexes Required for Transport / chemistry
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Hydrolysis
  • Nanotubes
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Unilamellar Liposomes


  • DID4 protein, S cerevisiae
  • Endosomal Sorting Complexes Required for Transport
  • SNF7 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Unilamellar Liposomes
  • VPS4 protein, S cerevisiae
  • Vps24 protein, S cerevisiae
  • Adenosine Triphosphate
  • Adenosine Triphosphatases