Reactive oxygen species regulate activity-dependent neuronal plasticity in Drosophila
- University of Cambridge, United Kingdom
- Janelia Research Campus, Howard Hughes Medical Institute, United States
- University of Manchester, United Kingdom
- University of York, United Kingdom
Abstract
Reactive oxygen species (ROS) have been extensively studied as damaging agents associated with ageing and neurodegenerative conditions. Their role in the nervous system under non-pathological conditions has remained poorly understood. Working with the Drosophila larval locomotor network, we show that in neurons ROS act as obligate signals required for neuronal activity-dependent structural plasticity, of both pre- and postsynaptic terminals. ROS signaling is also necessary for maintaining evoked synaptic transmission at the neuromuscular junction, and for activity-regulated homeostatic adjustment of motor network output, as measured by larval crawling behavior. We identified the highly conserved Parkinson's disease-linked protein DJ-1ß as a redox sensor in neurons where it regulates structural plasticity, in part via modulation of the PTEN-PI3Kinase pathway. This study provides a new conceptual framework of neuronal ROS as second messengers required for neuronal plasticity and for network tuning, whose dysregulation in the ageing brain and under neurodegenerative conditions may contribute to synaptic dysfunction.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Matthew C W Oswald
Funding
Biotechnology and Biological Sciences Research Council (BB/I01179X/1)
- Matthias Landgraf
Biotechnology and Biological Sciences Research Council (BB/M002934/1)
- Matthias Landgraf
Biotechnology and Biological Sciences Research Council (BB/I012273/1)
- Sean T Sweeney
Biotechnology and Biological Sciences Research Council (BB/M002322/1)
- Sean T Sweeney
Biotechnology and Biological Sciences Research Council (BB/N/014561/1)
- Richard A Baines
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Graeme W Davis, University of California, San Francisco, United States
Version history
- Received: June 20, 2018
- Accepted: December 12, 2018
- Accepted Manuscript published: December 12, 2018 (version 1)
- Accepted Manuscript updated: December 17, 2018 (version 2)
- Version of Record published: December 27, 2018 (version 3)
Copyright
© 2018, Oswald 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.
Metrics
-
- 7,923
- Page views
-
- 942
- Downloads
-
- 52
- Citations
Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Reactive oxygen species regulate activity-dependent neuronal plasticity in Drosophila
eLife 7:e39393.
https://doi.org/10.7554/eLife.39393
Further reading
-
- Neuroscience
Gradually reducing a source of fear during extinction treatments may weaken negative memories in the long term.
-
- Cell Biology
- Neuroscience
O-GlcNAcylation is a dynamic post-translational modification that diversifies the proteome. Its dysregulation is associated with neurological disorders that impair cognitive function, and yet identification of phenotype-relevant candidate substrates in a brain-region specific manner remains unfeasible. By combining an O-GlcNAc binding activity derived from Clostridium perfringens OGA (CpOGA) with TurboID proximity labeling in Drosophila, we developed an O-GlcNAcylation profiling tool that translates O-GlcNAc modification into biotin conjugation for tissue-specific candidate substrates enrichment. We mapped the O-GlcNAc interactome in major brain regions of Drosophila and found that components of the translational machinery, particularly ribosomal subunits, were abundantly O-GlcNAcylated in the mushroom body of Drosophila brain. Hypo-O-GlcNAcylation induced by ectopic expression of active CpOGA in the mushroom body decreased local translational activity, leading to olfactory learning deficits that could be rescued by dMyc overexpression-induced increase of protein synthesis. Our study provides a useful tool for future dissection of tissue-specific functions of O-GlcNAcylation in Drosophila, and suggests a possibility that O-GlcNAcylation impacts cognitive function via regulating regional translational activity in the brain.
