Autophagy promotes synapse development in Drosophila
Open accessAbstract
Autophagy, a lysosome-dependent degradation mechanism, mediates many biological processes, including cellular stress responses and neuroprotection. In this study, we demonstrate that autophagy positively regulates development of the Drosophila melanogaster larval neuromuscular junction (NMJ). Autophagy induces an NMJ overgrowth phenotype closely resembling that of highwire (hiw), an E3 ubiquitin ligase mutant. Moreover, like hiw, autophagy-induced NMJ overgrowth is suppressed by wallenda (wnd) and by a dominant-negative c-Jun NH2-terminal kinase (bskDN). We show that autophagy promotes NMJ growth by reducing Hiw levels. Thus, autophagy and the ubiquitin–proteasome system converge in regulating synaptic development. Because autophagy is triggered in response to many environmental cues, our findings suggest that it is perfectly positioned to link environmental conditions with synaptic growth and plasticity.
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Autophagy helps eliminate synapses during development.
“autophagy helps eliminate synapses during development [377,378]”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [377]
Autophagy has been implicated in synaptic remodeling in C. elegans and Drosophila.
“Autophagy has been implicated in synaptic remodeling in C. elegans (Rowland et al., 2006) and Drosophila (Shen and Ganetzky, 2009), but a role in mammalian synaptic development is unexplored.”
From Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits (2014) · cites this paper as Shen and Ganetzky, 2009
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“eliminate synapses during development [377,378], but can also accentuate axon degeneration during excitotoxic stress [375].”
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- Authors
- Shen, W., & Ganetzky, B.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Ganetzky, Barry
- ORCID
- Shen, Wei
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2009-09-28
- Volume
- 187
- Issue
- 1
- Pages
- 71-79
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2762098
- OpenAlex
- W2122791600
- Cited by
- 252
- References
- 34
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 18 · 2023: 10 · 2022: 14 · 2021: 22 · 2020: 21 · 2019: 20 · 2018: 16 · 2017: 14 · 2016: 19 · 2015: 11 · 2014: 7 · 2013: 13 · 2012: 17
- FWCI
- 9.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS15390, R01NS015390)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- autophagy, neuromuscular junction formation, synaptic development, Highwire, E3 ubiquitin ligase, c-Jun NH2-kinase, ubiquitin-proteasome system, Drosophila melanogaster, synaptic plasticity
- MeSH terms
- Amines, Animals, Autophagy, Drosophila, Fluorescent Dyes, Horseradish Peroxidase, Immunohistochemistry, Larva, Mutation, Nerve Tissue Proteins, Neuromuscular Junction, Synapses, Fluorescein-5-isothiocyanate, MAP Kinase Kinase Kinases, Drosophila Proteins, JNK Mitogen-Activated Protein Kinases
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