Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress
- University of California, San Francisco, United States
- The Salk Institute for Biological Studies, United States
Abstract
The inner nuclear membrane (INM) is a subdomain of the endoplasmic reticulum (ER) that is gated by the nuclear pore complex. It is unknown whether proteins of the INM and ER are degraded through shared or distinct pathways in mammalian cells. We applied dynamic proteomics to profile protein half-lives and report that INM and ER residents turn over at similar rates, indicating that the INM's unique topology is not a barrier to turnover. Using a microscopy approach, we observed that the proteasome can degrade INM proteins in situ. However, we also uncovered evidence for selective, vesicular transport-mediated turnover of a single INM protein, emerin, that is potentiated by ER stress. Emerin is rapidly cleared from the INM by a mechanism that requires emerin's LEM domain to mediate vesicular trafficking to lysosomes. This work demonstrates that the INM can be dynamically remodeled in response to environmental inputs.
Data availability
Raw and analyzed mass spectrometric data and associated scripts and tables have been deposited in Dryad. Analyzed data is also included with the manuscript as supplementary tables.
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Data from: Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stressDryad Digital Repository, doi.org/10.5061/dryad.n0r525h.
Article and author information
Author details
Abigail Buchwalter
Funding
NIH Office of the Director (NS096786)
- Martin Hetzer
National Institute of General Medical Sciences (R01GM126829)
- Martin Hetzer
National Cancer Institute (P30 014195)
- Martin Hetzer
Chapman Foundation
- Martin Hetzer
Helmsley Charitable Trust
- Martin Hetzer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Buchwalter 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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Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress
eLife 8:e49796.
https://doi.org/10.7554/eLife.49796
