Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress

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-liv...

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Bibliographic Details
Published in:eLife 2019-10, Vol.8
Main Authors: Buchwalter, Abigail, Schulte, Roberta, Tsai, Hsiao, Capitanio, Juliana, Hetzer, Martin
Format: Article
Language:English
Subjects:
Animals
Cell Biology
Cell division
Cell Line
Cytoplasmic Vesicles - metabolism
Deoxyribonucleic acid
DNA
Endoplasmic reticulum
Endoplasmic Reticulum Stress
ER stress
Lysosomes
Lysosomes - metabolism
Mammalian cells
Membrane proteins
Membrane Proteins - analysis
Mice
Myoblasts - chemistry
Myoblasts - physiology
nuclear envelope
Nuclear Envelope - chemistry
Nuclear Proteins - analysis
Peptides
Proteasomes
protein homeostasis
Protein Transport
Proteins
Proteome - analysis
Proteomics
Stains & staining
Trends
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.49796