A conserved and regulated mechanism drives endosomal Rab transition

  1. Lars Langemeyer
  2. Ann-Christin Borchers
  3. Eric Herrmann
  4. Nadia Füllbrunn
  5. Yaping Han
  6. Angela Perz
  7. Kathrin Auffarth
  8. Daniel Kümmel
  9. Christian Ungermann  Is a corresponding author
  1. University of Osnabrück, Germany
  2. University of Münster, Germany

Abstract

Endosomes and lysosomes harbor Rab5 and Rab7 on their surface as key proteins involved in their identity, biogenesis, and fusion. Rab activation requires a guanine nucleotide exchange factor (GEF), which is Mon1-Ccz1 for Rab7. During endosome maturation, Rab5 is replaced by Rab7, though the underlying mechanism remains poorly understood. Here, we identify the molecular determinants for Rab conversion in vivo and in vitro, and reconstitute Rab7 activation with yeast and metazoan proteins. We show (i) that Mon1-Ccz1 is an effector of Rab5, (ii) that membrane-bound Rab5 is the key factor to directly promote Mon1-Ccz1 dependent Rab7 activation and Rab7-dependent membrane fusion, and (iii) that this process is regulated in yeast by the casein kinase Yck3, which phosphorylates Mon1 and blocks Rab5 binding. Our study thus uncovers the minimal feed-forward machinery of the endosomal Rab cascade and a novel regulatory mechanism controlling this pathway.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Lars Langemeyer

    Department of Biology and Chemistry, Biochemistry section, University of Osnabrück, Osnabrück, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4309-0910
  2. Ann-Christin Borchers

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

    Department of Biochemistry, University of Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Nadia Füllbrunn

    Department of Biology and Chemistry, Biochemistry section, University of Osnabrück, Osnabrück, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Yaping Han

    Department of Biology and Chemistry, Biochemistry section, University of Osnabrück, Osnabrück, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Angela Perz

    Biology/Chemistry, University of Osnabrück, Osnabrück, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Kathrin Auffarth

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

    Department of Biochemistry, University of Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3950-5914
  9. 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 (SFB 944)

  • Christian Ungermann

Deutsche Forschungsgemeinschaft (SFB 944)

  • Daniel Kümmel

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

Reviewing Editor

  1. Suzanne R. Pfeffer, Stanford University School of Medicine, United States

Publication history

  1. Received: February 17, 2020
  2. Accepted: May 7, 2020
  3. Accepted Manuscript published: May 11, 2020 (version 1)
  4. Version of Record published: May 20, 2020 (version 2)

Copyright

© 2020, Langemeyer 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. Lars Langemeyer
  2. Ann-Christin Borchers
  3. Eric Herrmann
  4. Nadia Füllbrunn
  5. Yaping Han
  6. Angela Perz
  7. Kathrin Auffarth
  8. Daniel Kümmel
  9. Christian Ungermann
(2020)
A conserved and regulated mechanism drives endosomal Rab transition
eLife 9:e56090.
https://doi.org/10.7554/eLife.56090

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