An ESCRT-LEM protein surveillance system is poised to directly monitor the nuclear envelope and nuclear transport system.


Journal

eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614

Informations de publication

Date de publication:
03 04 2019
Historique:
received: 17 01 2019
accepted: 02 04 2019
pubmed: 4 4 2019
medline: 21 3 2020
entrez: 4 4 2019
Statut: epublish

Résumé

The integrity of the nuclear membranes coupled to the selective barrier of nuclear pore complexes (NPCs) are essential for the segregation of nucleoplasm and cytoplasm. Mechanical membrane disruption or perturbation to NPC assembly triggers an ESCRT-dependent surveillance system that seals nuclear pores: how these pores are sensed and sealed is ill defined. Using a budding yeast model, we show that the ESCRT Chm7 and the integral inner nuclear membrane (INM) protein Heh1 are spatially segregated by nuclear transport, with Chm7 being actively exported by Xpo1/Crm1. Thus, the exposure of the INM triggers surveillance with Heh1 locally activating Chm7. Sites of Chm7 hyperactivation show fenestrated sheets at the INM and potential membrane delivery at sites of nuclear envelope herniation. Our data suggest that perturbation to the nuclear envelope barrier would lead to local nuclear membrane remodeling to promote membrane sealing. Our findings have implications for disease mechanisms linked to NPC assembly and nuclear envelope integrity.

Identifiants

pubmed: 30942170
doi: 10.7554/eLife.45284
pii: 45284
pmc: PMC6461442
doi:
pii:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
Chm7 protein, S cerevisiae 0
Karyopherins 0
Membrane Proteins 0
Membrane Transport Proteins 0
Receptors, Cytoplasmic and Nuclear 0
Saccharomyces cerevisiae Proteins 0
Src1 protein, S cerevisiae 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : European Molecular Biology Organization
ID : Fellowship ALTF-1389-2016
Pays : International
Organisme : NIGMS NIH HHS
ID : T32 GM007223
Pays : United States
Organisme : European Molecular Biology Organization
ID : Fellowship 6885
Pays : International
Organisme : NIGMS NIH HHS
ID : R01 GM105672
Pays : United States
Organisme : NIH HHS
ID : GM105672
Pays : United States
Organisme : NIH HHS
ID : 5T32GM007223
Pays : United States

Informations de copyright

© 2019, Thaller et al.

Déclaration de conflit d'intérêts

DT, MA, SB, PR, MB, CL No competing interests declared

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Auteurs

David J Thaller (DJ)

Department of Cell Biology, Yale School of Medicine, New Haven, United States.

Matteo Allegretti (M)

Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse, Germany.

Sapan Borah (S)

Department of Cell Biology, Yale School of Medicine, New Haven, United States.

Paolo Ronchi (P)

Electron Microscopy Core Facility, European Molecular Biology Laboratory, Meyerhofstrasse, Germany.

Martin Beck (M)

Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse, Germany.

C Patrick Lusk (CP)

Department of Cell Biology, Yale School of Medicine, New Haven, United States.

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