Systematic functional analysis of Rab GTPases reveals limits of neuronal robustness to environmental challenges in flies
- Free University Berlin, Germany
- Freie Universität Berlin, Germany
- German Cancer Research Center (DKFZ) Heidelberg, Germany
- National Taiwan University, Taiwan
- German Cancer Research Center (DKFZ) and Heidelberg University, Germany
- 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.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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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.
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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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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