1. Biochemistry and Chemical Biology
  2. Cell Biology
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Molecular mechanism to target the endosomal Mon1-Ccz1 GEF complex to the pre-autophagosomal structure

  1. Jieqiong Gao
  2. Lars Langemeyer
  3. Daniel Kuemmel
  4. Fulvio Reggiori
  5. Christian Ungermann  Is a corresponding author
  1. University of Osnabrück, Germany
  2. University of Groningen, University Medical Center Groningen, Netherlands
Research Article
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Cite this article as: eLife 2018;7:e31145 doi: 10.7554/eLife.31145

Abstract

During autophagy, a newly formed double membrane surrounds its cargo to generate the so-called autophagosome, which then fuses with a lysosome after closure. Previous work implicated that endosomal Rab7/Ypt7 associates to autophagosomes prior to their fusion with lysosomes. Here, we unravel how the Mon1-Ccz1 guanosine exchange factor (GEF) acting upstream of Ypt7 is specifically recruited to the pre-autophagosomal structure under starvation conditions. We find that Mon1-Ccz1 directly binds to Atg8, the yeast homolog of the members of the mammalian LC3 protein family. This requires at least one LIR motif in the Ccz1 C-terminus, which is essential for autophagy but not for endosomal transport. In agreement, only wild-type, but not LIR-mutated Mon1-Ccz1 promotes Atg8-dependent activation of Ypt7. Our data reveal how GEF targeting can specify the fate of a newly formed organelle and provide new insights into the regulation of autophagosome-lysosome fusion.

Article and author information

Author details

  1. Jieqiong Gao

    Department of Biology and Chemistry, Biochemistry section, University of Osnabrück, Osnabrück, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Lars Langemeyer

    Department of Biology and Chemistry, Biochemistry section, University of Osnabrück, Osnabrück, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Daniel Kuemmel

    Department of Biology and Chemistry, Structural Biology section, University of Osnabrück, Osnabrück, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Fulvio Reggiori

    Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Christian Ungermann

    Department of Biology and Chemistry, Biochemistry section, University of Osnabrück, Osnabrück, Germany
    For correspondence
    cu@uos.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4331-8695

Funding

Deutsche Forschungsgemeinschaft (UN111/7-3)

  • Christian Ungermann

Deutsche Forschungsgemeinschaft (SFB 944)

  • Daniel Kuemmel

ZonMw (VICI 016.130.606)

  • Fulvio Reggiori

European Commission (Marie Skłodowska-Curie ITN)

  • Fulvio Reggiori

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF Sinergia (CRSII3_154421)

  • Fulvio Reggiori

Deutsche Forschungsgemeinschaft (SFB 944)

  • Christian Ungermann

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: August 9, 2017
  2. Accepted: February 12, 2018
  3. Accepted Manuscript published: February 15, 2018 (version 1)
  4. Version of Record published: March 7, 2018 (version 2)

Copyright

© 2018, Gao 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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