Systematic functional analysis of Rab GTPases reveals limits of neuronal robustness to environmental challenges in flies

  1. Friederike Elisabeth Kohrs
  2. Ilsa-Maria Daumann
  3. Bojana Pavlovic
  4. Eugene Jennifer Jin
  5. F. Ridvan Kiral
  6. Shih-Ching Lin
  7. Filip Port
  8. Heike Wolfenberg
  9. Thomas F Mathejczyk
  10. Gerit A Linneweber
  11. Chih-Chiang Chan
  12. Michael Boutros
  13. P Robin Hiesinger  Is a corresponding author
  1. Free University Berlin, Germany
  2. Freie Universität Berlin, Germany
  3. German Cancer Research Center (DKFZ) Heidelberg, Germany
  4. National Taiwan University, Taiwan
  5. German Cancer Research Center (DKFZ) and Heidelberg University, Germany
  6. Institute for Biology Free University Berlin, Germany

Abstract

Rab GTPases are molecular switches that regulate membrane trafficking in all cells. Neurons have particular demands on membrane trafficking and express numerous Rab GTPases of unknown function. Here we report the generation and characterization of molecularly defined null mutants for all 26 rab genes in Drosophila. In flies, all rab genes are expressed in the nervous system where at least half exhibit particularly high levels compared to other tissues. Surprisingly, loss of any of these 13 nervous system-enriched Rabs yielded viable and fertile flies without obvious morphological defects. However, all 13 mutants differentially affected development when challenged with different temperatures, or neuronal function when challenged with continuous stimulation. We identified a synaptic maintenance defect following continuous stimulation for six mutants, including an autophagy-independent role of rab26. The complete mutant collection generated in this study provides a basis for further comprehensive studies of Rab GTPases during development and function in vivo.

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. Friederike Elisabeth Kohrs

    Division of Neurobiology, Institute for Biology, Free University Berlin, Berlin, Germany
    Competing interests
    No competing interests declared.
  2. Ilsa-Maria Daumann

    Division of Neurobilogy, Freie Universität Berlin, Berlin, Germany
    Competing interests
    No competing interests declared.
  3. Bojana Pavlovic

    Div. Signaling and Functional Genomics and Heidelberg University, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany
    Competing interests
    No competing interests declared.
  4. Eugene Jennifer Jin

    Division of Neurobilogy, Freie Universität Berlin, Berlin, Germany
    Competing interests
    No competing interests declared.
  5. F. Ridvan Kiral

    Division of Neurobilogy, Freie Universität Berlin, Berlin, Germany
    Competing interests
    No competing interests declared.
  6. Shih-Ching Lin

    Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2960-5348
  7. Filip Port

    Div. Signaling and Functional Genomics and Heidelberg University, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5157-4835
  8. Heike Wolfenberg

    Division of Neurobilogy, Freie Universität Berlin, Berlin, Germany
    Competing interests
    No competing interests declared.
  9. Thomas F Mathejczyk

    Division of Neurobilogy, Freie Universität Berlin, Berlin, Germany
    Competing interests
    No competing interests declared.
  10. Gerit A Linneweber

    Division of Neurobiology, Institute for Biology, Free University Berlin, Berlin, Germany
    Competing interests
    No competing interests declared.
  11. Chih-Chiang Chan

    Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2626-3805
  12. Michael Boutros

    Division Signaling and Functional Genomics, German Cancer Research Center (DKFZ) and Heidelberg University, Heidelberg, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9458-817X
  13. P Robin Hiesinger

    Division of Neurobiology, Institute for Biology Free University Berlin, Berlin, Germany
    For correspondence
    prh@zedat.fu-berlin.de
    Competing interests
    P Robin Hiesinger, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4698-3527

Funding

Deutsche Forschungsgemeinschaft (TRR186)

  • P Robin Hiesinger

Deutsche Forschungsgemeinschaft (TRR186)

  • Michael Boutros

National Institutes of Health (RO1EY018884)

  • P Robin Hiesinger

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

Reviewing Editor

  1. Mani Ramaswami, Trinity College Dublin, Ireland

Publication history

  1. Received: June 2, 2020
  2. Accepted: March 4, 2021
  3. Accepted Manuscript published: March 5, 2021 (version 1)
  4. Version of Record published: April 1, 2021 (version 2)

Copyright

© 2021, Kohrs 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. Friederike Elisabeth Kohrs
  2. Ilsa-Maria Daumann
  3. Bojana Pavlovic
  4. Eugene Jennifer Jin
  5. F. Ridvan Kiral
  6. Shih-Ching Lin
  7. Filip Port
  8. Heike Wolfenberg
  9. Thomas F Mathejczyk
  10. Gerit A Linneweber
  11. Chih-Chiang Chan
  12. Michael Boutros
  13. P Robin Hiesinger
(2021)
Systematic functional analysis of Rab GTPases reveals limits of neuronal robustness to environmental challenges in flies
eLife 10:e59594.
https://doi.org/10.7554/eLife.59594

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