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

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 gen...

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Main Authors: Friederike E Kohrs, Ilsa-Maria Daumann, Bojana Pavlovic, Eugene Jennifer Jin, F Ridvan Kiral, Shih-Ching Lin, Filip Port, Heike Wolfenberg, Thomas F Mathejczyk, Gerit A Linneweber, Chih-Chiang Chan, Michael Boutros, P Robin Hiesinger
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2021-03-01
Series:eLife
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Online Access:https://elifesciences.org/articles/59594
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author Friederike E Kohrs
Ilsa-Maria Daumann
Bojana Pavlovic
Eugene Jennifer Jin
F Ridvan Kiral
Shih-Ching Lin
Filip Port
Heike Wolfenberg
Thomas F Mathejczyk
Gerit A Linneweber
Chih-Chiang Chan
Michael Boutros
P Robin Hiesinger
author_facet Friederike E Kohrs
Ilsa-Maria Daumann
Bojana Pavlovic
Eugene Jennifer Jin
F Ridvan Kiral
Shih-Ching Lin
Filip Port
Heike Wolfenberg
Thomas F Mathejczyk
Gerit A Linneweber
Chih-Chiang Chan
Michael Boutros
P Robin Hiesinger
author_sort Friederike E Kohrs
collection DOAJ
description 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.
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spelling doaj.art-1d73470d06fd4145826f1e3724bfe42d2022-12-22T03:37:47ZengeLife Sciences Publications LtdeLife2050-084X2021-03-011010.7554/eLife.59594Systematic functional analysis of rab GTPases reveals limits of neuronal robustness to environmental challenges in fliesFriederike E Kohrs0Ilsa-Maria Daumann1Bojana Pavlovic2Eugene Jennifer Jin3F Ridvan Kiral4Shih-Ching Lin5https://orcid.org/0000-0003-2960-5348Filip Port6https://orcid.org/0000-0002-5157-4835Heike Wolfenberg7Thomas F Mathejczyk8Gerit A Linneweber9Chih-Chiang Chan10https://orcid.org/0000-0003-2626-3805Michael Boutros11https://orcid.org/0000-0002-9458-817XP Robin Hiesinger12https://orcid.org/0000-0003-4698-3527Division of Neurobiology, Institute for Biology, Freie Universität Berlin, Berlin, GermanyDivision of Neurobiology, Institute for Biology, Freie Universität Berlin, Berlin, GermanyGerman Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics and Heidelberg University, Heidelberg, GermanyDivision of Neurobiology, Institute for Biology, Freie Universität Berlin, Berlin, GermanyDivision of Neurobiology, Institute for Biology, Freie Universität Berlin, Berlin, GermanyNational Taiwan University, Taipei, TaiwanGerman Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics and Heidelberg University, Heidelberg, GermanyDivision of Neurobiology, Institute for Biology, Freie Universität Berlin, Berlin, GermanyDivision of Neurobiology, Institute for Biology, Freie Universität Berlin, Berlin, GermanyDivision of Neurobiology, Institute for Biology, Freie Universität Berlin, Berlin, GermanyNational Taiwan University, Taipei, TaiwanGerman Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics and Heidelberg University, Heidelberg, GermanyDivision of Neurobiology, Institute for Biology, Freie Universität Berlin, Berlin, GermanyRab 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.https://elifesciences.org/articles/59594Rab GTPasemutant collectionDrosophila
spellingShingle Friederike E Kohrs
Ilsa-Maria Daumann
Bojana Pavlovic
Eugene Jennifer Jin
F Ridvan Kiral
Shih-Ching Lin
Filip Port
Heike Wolfenberg
Thomas F Mathejczyk
Gerit A Linneweber
Chih-Chiang Chan
Michael Boutros
P Robin Hiesinger
Systematic functional analysis of rab GTPases reveals limits of neuronal robustness to environmental challenges in flies
eLife
Rab GTPase
mutant collection
Drosophila
title Systematic functional analysis of rab GTPases reveals limits of neuronal robustness to environmental challenges in flies
title_full Systematic functional analysis of rab GTPases reveals limits of neuronal robustness to environmental challenges in flies
title_fullStr Systematic functional analysis of rab GTPases reveals limits of neuronal robustness to environmental challenges in flies
title_full_unstemmed Systematic functional analysis of rab GTPases reveals limits of neuronal robustness to environmental challenges in flies
title_short Systematic functional analysis of rab GTPases reveals limits of neuronal robustness to environmental challenges in flies
title_sort systematic functional analysis of rab gtpases reveals limits of neuronal robustness to environmental challenges in flies
topic Rab GTPase
mutant collection
Drosophila
url https://elifesciences.org/articles/59594
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