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

  1. Abigail Buchwalter  Is a corresponding author
  2. Roberta Schulte
  3. Hsiao Tsai
  4. Juliana Capitanio
  5. Martin Hetzer  Is a corresponding author
  1. University of California, San Francisco, United States
  2. 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.

The following data sets were generated

Article and author information

Author details

  1. Abigail Buchwalter

    Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States
    For correspondence
    abigail.buchwalter@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7181-6961
  2. Roberta Schulte

    Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Hsiao Tsai

    Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Juliana Capitanio

    Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Martin Hetzer

    Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, United States
    For correspondence
    hetzer@salk.edu
    Competing interests
    The authors declare that no competing interests exist.

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.

Reviewing Editor

  1. Elizabeth A Miller, MRC Laboratory of Molecular Biology, United Kingdom

Publication history

  1. Received: June 29, 2019
  2. Accepted: October 9, 2019
  3. Accepted Manuscript published: October 10, 2019 (version 1)
  4. Version of Record published: October 21, 2019 (version 2)

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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  1. Abigail Buchwalter
  2. Roberta Schulte
  3. Hsiao Tsai
  4. Juliana Capitanio
  5. Martin Hetzer
(2019)
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

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