Full length RTN3 regulates turnover of tubular endoplasmic reticulum via selective autophagy

  1. Paolo Grumati
  2. Giulio Morozzi
  3. Soraya Hölper
  4. Muriel Mari
  5. Marie-Lena IE Harwardt
  6. Riqiang Yan
  7. Stefan Müller
  8. Fulvio Reggiori
  9. Mike Heilemann
  10. Ivan Dikic  Is a corresponding author
  1. Goethe University School of Medicine, Germany
  2. University of Groningen, University Medical Center Groningen, Netherlands
  3. Goethe University Frankfurt, Germany
  4. Lerner Research Institute, United States

Abstract

The turnover of endoplasmic reticulum (ER) ensures the correct biological activity of its distinct domains. In mammalian cells the ER is degraded via a selective autophagy pathway (ER-phagy), mediated by two specific receptors: FAM134B, responsible for the turnover of ER sheets and SEC62 that regulates ER recovery following stress. Here we identified reticulon 3 (RTN3) as a specific receptor for the degradation of ER tubules. Oligomerization of the long isoform of RTN3 is sufficient to trigger fragmentation of ER tubules. The long N-terminal region of RTN3 contains several newly identified LC3-interacting regions (LIR). Binding to LC3s/GABARAPs is essential for the fragmentation of ER tubules and their delivery to lysosomes. RTN3-mediated ER-phagy requires conventional autophagy components, but is independent of FAM134B. None of the other reticulon family members have the ability to induce fragmentation of ER tubules during starvation. Therefore, we assign a unique function to RTN3 during autophagy.

Article and author information

Author details

  1. Paolo Grumati

    Institute of Biochemistry II, Goethe University School of Medicine, Frankfurt am Main, Germany
    Competing interests
    No competing interests declared.
  2. Giulio Morozzi

    Institute of Biochemistry II, Goethe University School of Medicine, Frankfurt am Main, Germany
    Competing interests
    No competing interests declared.
  3. Soraya Hölper

    Institute of Biochemistry II, Goethe University School of Medicine, Frankfurt am Main, Germany
    Competing interests
    No competing interests declared.
  4. Muriel Mari

    Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
  5. Marie-Lena IE Harwardt

    Institute of Physical and Theoretical Chemistry, Goethe University Frankfurt, Frankfurt am Main, Germany
    Competing interests
    No competing interests declared.
  6. Riqiang Yan

    Department of Neurosciences, Lerner Research Institute, Cleveland, United States
    Competing interests
    No competing interests declared.
  7. Stefan Müller

    Institute of Biochemistry II, Goethe University School of Medicine, Frankfurt am Main, Germany
    Competing interests
    No competing interests declared.
  8. Fulvio Reggiori

    Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
  9. Mike Heilemann

    Institute of Physical and Theoretical Chemistry, Goethe University Frankfurt, Frankfurt am Main, Germany
    Competing interests
    No competing interests declared.
  10. Ivan Dikic

    Institute of Biochemistry II, Goethe University Frankfurt, Frankfurt am Main, Germany
    For correspondence
    dikic@biochem2.uni-frankfurt.de
    Competing interests
    Ivan Dikic, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8156-9511

Funding

Deutsche Forschungsgemeinschaft (Collaborative Research Centre on Selective Autophagy SFB 1177)

  • Mike Heilemann
  • Ivan Dikic

Cluster of Excellence Goethe University Frankfurt am Main (EXC 115)

  • Mike Heilemann
  • Ivan Dikic

LOEWE programme (Network Ub-Net)

  • Ivan Dikic

LOEWE Center for Gene and Cell Therapy Frankfurt (CGT)

  • Ivan Dikic

7.FP, COFUND, Goethe International Postdoc Program GO-IN (No 291776)

  • Paolo Grumati

SNF Sinergia (CRSII#_154421)

  • Fulvio Reggiori

ZonMw (VICI (016.130.606))

  • Fulvio Reggiori

Marie Sklodowska-Curie Cofund

  • Fulvio Reggiori

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Hong Zhang, Institute of Biophysics, Chinese Academy of Sciences, China

Publication history

  1. Received: February 2, 2017
  2. Accepted: June 14, 2017
  3. Accepted Manuscript published: June 15, 2017 (version 1)
  4. Version of Record published: July 19, 2017 (version 2)

Copyright

© 2017, Grumati 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. Paolo Grumati
  2. Giulio Morozzi
  3. Soraya Hölper
  4. Muriel Mari
  5. Marie-Lena IE Harwardt
  6. Riqiang Yan
  7. Stefan Müller
  8. Fulvio Reggiori
  9. Mike Heilemann
  10. Ivan Dikic
(2017)
Full length RTN3 regulates turnover of tubular endoplasmic reticulum via selective autophagy
eLife 6:e25555.
https://doi.org/10.7554/eLife.25555

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