ESCRT-III activation by parallel action of ESCRT-I/II and ESCRT-0/Bro1 during MVB biogenesis

  1. Shaogeng Tang
  2. Nicholas J Buchkovich
  3. W Mike Henne
  4. Sudeep Banjade
  5. Yun Jung Kim
  6. Scott D Emr  Is a corresponding author
  1. Cornell University, United States
  2. The Pennsylvania State University College of Medicine, United States
  3. The University of Texas Southwestern Medical Center, United States

Abstract

The endosomal sorting complexes required for transport (ESCRT) pathway facilitates multiple fundamental membrane remodeling events. Previously, we determined X-ray crystal structures of the ESCRT-III subunit, the yeast CHMP4 ortholog, Snf7, in its active and polymeric state (Tang et al., 2015). However, how ESCRT-III activation is coordinated by the upstream ESCRT components at endosomes remains unclear. Here, we provide a molecular explanation for the functional divergence of structurally similar ESCRT-III subunits. We characterize novel mutations in ESCRT-III Snf7 that trigger activation, and identify a novel role of the yeast ALIX ortholog, Bro1, in Snf7 assembly. We show that upstream ESCRTs regulate Snf7 activation at both its N-terminal core domain and the C-terminus α6 helix through two parallel ubiquitin-dependent pathways: the ESCRT-I-ESCRT-II-Vps20 pathway and the ESCRT-0-Bro1 pathway. We therefore provide an enhanced understanding for the activation of the spatially unique ESCRT-III-mediated membrane remodeling.

Article and author information

Author details

  1. Shaogeng Tang

    Weill Institute of Cell and Molecuar Biology, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Nicholas J Buchkovich

    Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. W Mike Henne

    Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Sudeep Banjade

    Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Yun Jung Kim

    Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Scott D Emr

    Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States
    For correspondence
    sde26@cornell.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. William I Weis, Stanford University, United States

Publication history

  1. Received: February 26, 2016
  2. Accepted: April 11, 2016
  3. Accepted Manuscript published: April 13, 2016 (version 1)
  4. Version of Record published: May 12, 2016 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Shaogeng Tang
  2. Nicholas J Buchkovich
  3. W Mike Henne
  4. Sudeep Banjade
  5. Yun Jung Kim
  6. Scott D Emr
(2016)
ESCRT-III activation by parallel action of ESCRT-I/II and ESCRT-0/Bro1 during MVB biogenesis
eLife 5:e15507.
https://doi.org/10.7554/eLife.15507
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