1. Cell Biology
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The ULK1-FBXW5-SEC23B nexus controls autophagy

  1. Yeon-Tae Jeong
  2. Daniele Simoneschi
  3. Sarah Keegan
  4. David Melville
  5. Natalia S Adler
  6. Anita Saraf
  7. Laurence Florens
  8. Michael P Washburn
  9. Claudio N Cavasotto
  10. David Fenyö
  11. Ana Maria Cuervo
  12. Mario Rossi  Is a corresponding author
  13. Michele Pagano  Is a corresponding author
  1. New York University School of Medicine, United States
  2. Howard Hughes Medical Institute, University of California, Berkeley, United States
  3. Instituto de Investigación en Biomedicina de Buenos Aires, CONICET-Partner Institute of the Max Planck Society, Argentina
  4. The Stowers Institute for Medical Research, United States
  5. Albert Einstein College of Medicine, United States
Research Article
  • Cited 2
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Cite this article as: eLife 2018;7:e42253 doi: 10.7554/eLife.42253

Abstract

In response to nutrient deprivation, the cell mobilizes an extensive amount of membrane to form and grow the autophagosome, allowing the progression of autophagy. By providing membranes and stimulating LC3 lipidation, COPII (Coat Protein Complex II) promotes autophagosome biogenesis. Here, we show that the F-box protein FBXW5 targets SEC23B, a component of COPII, for proteasomal degradation and that this event limits the autophagic flux in the presence of nutrients. In response to starvation, ULK1 phosphorylates SEC23B on Serine 186, preventing the interaction of SEC23B with FBXW5 and, therefore, inhibiting SEC23B degradation. Phosphorylated and stabilized SEC23B associates with SEC24A and SEC24B, but not SEC24C and SEC24D, and they re-localize to the ER-Golgi intermediate compartment, promoting autophagic flux. We propose that, in the presence of nutrients, FBXW5 limits COPII-mediated autophagosome biogenesis. Inhibition of this event by ULK1 ensures efficient execution of the autophagic cascade in response to nutrient starvation.

Article and author information

Author details

  1. Yeon-Tae Jeong

    Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Daniele Simoneschi

    Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sarah Keegan

    Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. David Melville

    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Natalia S Adler

    Instituto de Investigación en Biomedicina de Buenos Aires, CONICET-Partner Institute of the Max Planck Society, Buenos Aires, Argentina
    Competing interests
    The authors declare that no competing interests exist.
  6. Anita Saraf

    The Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Laurence Florens

    The Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Michael P Washburn

    The Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7568-2585
  9. Claudio N Cavasotto

    Instituto de Investigación en Biomedicina de Buenos Aires, CONICET-Partner Institute of the Max Planck Society, Buenos Aires, Argentina
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1372-0379
  10. David Fenyö

    Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5049-3825
  11. Ana Maria Cuervo

    Department of DevelopmentalandMolecular Biology, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Mario Rossi

    Instituto de Investigación en Biomedicina de Buenos Aires, CONICET-Partner Institute of the Max Planck Society, Buenos Aires, Argentina
    For correspondence
    mrossi@ibioba-mpsp-conicet.gov.ar
    Competing interests
    The authors declare that no competing interests exist.
  13. Michele Pagano

    Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States
    For correspondence
    michele.pagano@nyumc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3210-2442

Funding

National Institutes of Health (R01‐CA076584)

  • Michele Pagano

National Institutes of Health (R01‐GM057587)

  • Michele Pagano

Agencia Nacional de Promoción Científica y Tecnológica (PICT‐2014‐0458)

  • Mario Rossi

Agencia Nacional de Promoción Científica y Tecnológica (PICT2016‐2620)

  • Mario Rossi

Agencia Nacional de Promoción Científica y Tecnológica (PICT‐ 2014‐3599)

  • Claudio N Cavasotto

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

Reviewing Editor

  1. Noboru Mizushima, The University of Tokyo, Japan

Publication history

  1. Received: September 25, 2018
  2. Accepted: December 27, 2018
  3. Accepted Manuscript published: December 31, 2018 (version 1)
  4. Version of Record published: January 29, 2019 (version 2)

Copyright

© 2018, Jeong 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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