Sec24 phosphorylation regulates autophagosome abundance during nutrient deprivation

  1. Saralin Davis
  2. Juan Wang
  3. Ming Zhu
  4. Kyle Stahmer
  5. Ramya Lakshminarayan
  6. Majid Ghassemian
  7. Yu Jiang
  8. Elizabeth A Miller
  9. Susan Ferro-Novick  Is a corresponding author
  1. University of California, San Diego, United States
  2. Columbia University, United States
  3. University of Pittsburgh School of Medicine, United States

Abstract

Endoplasmic Reticulum (ER)-derived COPII coated vesicles constitutively transport secretory cargo to the Golgi. However, during starvation-induced stress, COPII vesicles have been implicated as a membrane source for autophagosomes, distinct organelles that engulf cellular components for degradation by macroautophagy (hereafter called autophagy). How cells regulate core trafficking machinery to fulfill dramatically different cellular roles in response to environmental cues is unknown. Here we show that phosphorylation of conserved amino acids on the membrane-distal surface of the Saccharomyces cerevisiae COPII cargo adaptor, Sec24, reprograms COPII vesicles for autophagy. We also show casein kinase 1 (Hrr25) is a key kinase that phosphorylates this regulatory surface. During autophagy, Sec24 phosphorylation regulates autophagosome number and its interaction with the C-terminus of Atg9, a component of the autophagy machinery required for autophagosome initiation. We propose that the acute need to produce autophagosomes during starvation drives the interaction of Sec24 with Atg9 to increase autophagosome abundance.

Article and author information

Author details

  1. Saralin Davis

    Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9834-8683
  2. Juan Wang

    Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ming Zhu

    Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Kyle Stahmer

    Department of Biological Sciences, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ramya Lakshminarayan

    Department of Biological Sciences, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Majid Ghassemian

    Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Yu Jiang

    Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Elizabeth A Miller

    Department of Biological Sciences, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Susan Ferro-Novick

    Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
    For correspondence
    sfnovick@ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8714-7352

Funding

National Institute of General Medical Sciences (GM114111)

  • Saralin Davis
  • Juan Wang
  • Susan Ferro-Novick

National Cancer Institute (CA169186)

  • Yu Jiang

National Institute of General Medical Sciences (GM085089)

  • Kyle Stahmer
  • Ramya Lakshminarayan
  • Elizabeth A Miller

National Institute of General Medical Sciences (GM115422)

  • Saralin Davis
  • Juan Wang
  • Susan Ferro-Novick

Medical Research Council (MC_UP_1201/10)

  • Elizabeth A Miller

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 1, 2016
  2. Accepted: November 14, 2016
  3. Accepted Manuscript published: November 18, 2016 (version 1)
  4. Version of Record published: December 8, 2016 (version 2)

Copyright

© 2016, Davis 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. Saralin Davis
  2. Juan Wang
  3. Ming Zhu
  4. Kyle Stahmer
  5. Ramya Lakshminarayan
  6. Majid Ghassemian
  7. Yu Jiang
  8. Elizabeth A Miller
  9. Susan Ferro-Novick
(2016)
Sec24 phosphorylation regulates autophagosome abundance during nutrient deprivation
eLife 5:e21167.
https://doi.org/10.7554/eLife.21167
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