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

The endosomal sorting complexes required for transport (ESCRT) pathway facilitates multiple fundamental membrane remodeling events. Previously, we determined X-ray crystal structures of ESCRT-III subunit Snf7, the yeast CHMP4 ortholog, in its active and polymeric state (Tang et al., 2015). However,...

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Main Authors: Shaogeng Tang, Nicholas J Buchkovich, W Mike Henne, Sudeep Banjade, Yun Jung Kim, Scott D Emr
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2016-04-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/15507
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author Shaogeng Tang
Nicholas J Buchkovich
W Mike Henne
Sudeep Banjade
Yun Jung Kim
Scott D Emr
author_facet Shaogeng Tang
Nicholas J Buchkovich
W Mike Henne
Sudeep Banjade
Yun Jung Kim
Scott D Emr
author_sort Shaogeng Tang
collection DOAJ
description The endosomal sorting complexes required for transport (ESCRT) pathway facilitates multiple fundamental membrane remodeling events. Previously, we determined X-ray crystal structures of ESCRT-III subunit Snf7, the yeast CHMP4 ortholog, 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 Bro1, the yeast ALIX ortholog, 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.
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spelling doaj.art-fe94cbe0e65e461bbec9cd9f7ae267c12022-12-22T02:05:18ZengeLife Sciences Publications LtdeLife2050-084X2016-04-01510.7554/eLife.15507ESCRT-III activation by parallel action of ESCRT-I/II and ESCRT-0/Bro1 during MVB biogenesisShaogeng Tang0https://orcid.org/0000-0002-3904-492XNicholas J Buchkovich1W Mike Henne2Sudeep Banjade3Yun Jung Kim4Scott D Emr5https://orcid.org/0000-0002-5408-6781Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States; Department of Molecular Biology and Genetics, Cornell University, Ithaca, United StatesWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States; Department of Molecular Biology and Genetics, Cornell University, Ithaca, United StatesWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States; Department of Molecular Biology and Genetics, Cornell University, Ithaca, United StatesWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States; Department of Molecular Biology and Genetics, Cornell University, Ithaca, United StatesWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States; Department of Molecular Biology and Genetics, Cornell University, Ithaca, United StatesWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States; Department of Molecular Biology and Genetics, Cornell University, Ithaca, United StatesThe endosomal sorting complexes required for transport (ESCRT) pathway facilitates multiple fundamental membrane remodeling events. Previously, we determined X-ray crystal structures of ESCRT-III subunit Snf7, the yeast CHMP4 ortholog, 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 Bro1, the yeast ALIX ortholog, 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.https://elifesciences.org/articles/15507ESCRT-IIISnf7activationBro1ESCRT-IESCRT-II
spellingShingle Shaogeng Tang
Nicholas J Buchkovich
W Mike Henne
Sudeep Banjade
Yun Jung Kim
Scott D Emr
ESCRT-III activation by parallel action of ESCRT-I/II and ESCRT-0/Bro1 during MVB biogenesis
eLife
ESCRT-III
Snf7
activation
Bro1
ESCRT-I
ESCRT-II
title ESCRT-III activation by parallel action of ESCRT-I/II and ESCRT-0/Bro1 during MVB biogenesis
title_full ESCRT-III activation by parallel action of ESCRT-I/II and ESCRT-0/Bro1 during MVB biogenesis
title_fullStr ESCRT-III activation by parallel action of ESCRT-I/II and ESCRT-0/Bro1 during MVB biogenesis
title_full_unstemmed ESCRT-III activation by parallel action of ESCRT-I/II and ESCRT-0/Bro1 during MVB biogenesis
title_short ESCRT-III activation by parallel action of ESCRT-I/II and ESCRT-0/Bro1 during MVB biogenesis
title_sort escrt iii activation by parallel action of escrt i ii and escrt 0 bro1 during mvb biogenesis
topic ESCRT-III
Snf7
activation
Bro1
ESCRT-I
ESCRT-II
url https://elifesciences.org/articles/15507
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AT wmikehenne escrtiiiactivationbyparallelactionofescrtiiiandescrt0bro1duringmvbbiogenesis
AT sudeepbanjade escrtiiiactivationbyparallelactionofescrtiiiandescrt0bro1duringmvbbiogenesis
AT yunjungkim escrtiiiactivationbyparallelactionofescrtiiiandescrt0bro1duringmvbbiogenesis
AT scottdemr escrtiiiactivationbyparallelactionofescrtiiiandescrt0bro1duringmvbbiogenesis