Structure of cellular ESCRT-III spirals and their relationship to HIV budding

  1. Anil G Cashikar
  2. Soomin Shim
  3. Robyn Roth
  4. Michael R Maldazys
  5. John E Heuser
  6. Phyllis I Hanson  Is a corresponding author
  1. Washington University School of Medicine, United States

Abstract

The ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission for trafficking into multivesicular bodies in the endocytic pathway and for the topologically related processes of viral budding and cytokinesis, but how they accomplish this remains unclear. Using deep-etch electron microscopy, we find that endogenous ESCRT-III filaments stabilized by depleting cells of Vps4 create uniform membrane-deforming conical spirals which are assemblies of specific ESCRT-III heteropolymers. To explore functional roles for ESCRT-III filaments, we examine HIV-1 Gag-mediated budding of virus-like particles and find that depleting Vps4 traps ESCRT-III filaments around nascent Gag assemblies. Interpolating between the observed structures suggests a new role for Vps4 in separating ESCRT-III from Gag or other cargo to allow centripetal growth of a neck constricting ESCRT-III spiral.

Article and author information

Author details

  1. Anil G Cashikar

    Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Soomin Shim

    Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Robyn Roth

    Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Michael R Maldazys

    Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. John E Heuser

    Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Phyllis I Hanson

    Washington University School of Medicine, St. Louis, United States
    For correspondence
    phanson22@WUSTL.EDU
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Wesley Sundquist, University of Utah, United States

Version history

  1. Received: December 30, 2013
  2. Accepted: May 27, 2014
  3. Accepted Manuscript published: May 30, 2014 (version 1)
  4. Version of Record published: July 1, 2014 (version 2)

Copyright

© 2014, Cashikar et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Anil G Cashikar
  2. Soomin Shim
  3. Robyn Roth
  4. Michael R Maldazys
  5. John E Heuser
  6. Phyllis I Hanson
(2014)
Structure of cellular ESCRT-III spirals and their relationship to HIV budding
eLife 3:e02184.
https://doi.org/10.7554/eLife.02184

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https://doi.org/10.7554/eLife.02184