An ESCRT-LEM protein surveillance system is poised to directly monitor the nuclear envelope and nuclear transport system
- Yale School of Medicine, United States
- European Molecular Biology Laboratory, Germany
Abstract
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.
Data availability
All data generated and analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figure 3.
Article and author information
Author details
Funding
National Institutes of Health (GM105672)
- C Patrick Lusk
European Molecular Biology Organization (Fellowship 6885)
- David J Thaller
European Molecular Biology Organization (Fellowship ALTF-1389-2016)
- Matteo Allegretti
National Institutes of Health (5T32GM007223)
- David J Thaller
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Thaller 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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An ESCRT-LEM protein surveillance system is poised to directly monitor the nuclear envelope and nuclear transport system
eLife 8:e45284.
https://doi.org/10.7554/eLife.45284
