ArticleThe Journal of cell biology2014
Reduced synaptic vesicle protein degradation at lysosomes curbs TBC1D24/sky-induced neurodegeneration.
Article in The Journal of cell biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
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Who cites it
62 citing papers in PubMed, 102 citations in OpenAlex.
- Analysis in vivo using a new method, ARGO (Analysis of Red-Green Offset), reveals complexity and cell-type specificity in presynaptic turnover of synaptic vesicle protein Synaptogyrin/SNG-1.Molecular biology of the cell · 2026Article
- Risperidone induces osteoporosis and neuropsychiatric treatment resistance via SMPD1-lysosome-mediated ferroptosis: dual rescue by active vitamin D analog ED-71.Journal of advanced research · 2026Article
- Review
- AnalysisbioRxiv : the preprint server for biology · 2025Article
- Soma-localized Rab39 inhibits synaptic autophagy by controlling trafficking of Atg9 vesicles.The EMBO journal · 2025Article
- Expansion of lysosomal capacity in early adult neurons driven by TFEB/HLH-30 protects dendrite maintenance during aging in Caenorhabditis elegans.PLoS biology · 2025Article
- Intersectin and endophilin condensates prime synaptic vesicles for release site replenishment.Nature neuroscience · 2025Article
- The involvement of the synaptic vesicle cycle in homocysteine induced neurotoxicity in vitro and in vivo.Scientific reports · 2025Article
- Article
- Chloroquine Affects Presynaptic Membrane Retrieval in Diaphragm Neuromuscular Junctions of Old Mice.International journal of molecular sciences · 2024Article
- Article
- Interaction between the TBC1D24 TLDc domain and the KIBRA C2 domain is disrupted by two epilepsy-associated TBC1D24 missense variants.The Journal of biological chemistry · 2024Article
- Review
- Deep orange gene editing triggers temperature-sensitive lethal phenotypes in Ceratitis capitata.BMC biotechnology · 2024Article
- Article
- The Putative Drosophila TMEM184B Ortholog Tmep Ensures Proper Locomotion by Restraining Ectopic Firing at the Neuromuscular Junction.Molecular neurobiology · 2022Article
- Genetic architecture and phenotypic landscape of deafness and onychodystrophy syndromes.Human genetics · 2022Review
- Synaptic Vesicle Recycling and the Endolysosomal System: A Reappraisal of Form and Function.Frontiers in synaptic neuroscience · 2022Review
- Organization of Presynaptic Autophagy-Related Processes.Frontiers in synaptic neuroscience · 2022Review
- Opposing functions for retromer and Rab11 in extracellular vesicle traffic at presynaptic terminals.The Journal of cell biology · 2021Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synaptic demise and accumulation of dysfunctional proteins are thought of as common features in neurodegeneration. However, the mechanisms by which synaptic proteins turn over remain elusive. In this paper, we study Drosophila melanogaster lacking active TBC1D24/Skywalker (Sky), a protein that in humans causes severe neurodegeneration, epilepsy, and DOOR (deafness, onychdystrophy, osteodystrophy, and mental retardation) syndrome, and identify endosome-to-lysosome trafficking as a mechanism for degradation of synaptic vesicle-associated proteins. In fly sky mutants, synaptic vesicles traveled excessively to endosomes. Using chimeric fluorescent timers, we show that synaptic vesicle-associated proteins were younger on average, suggesting that older proteins are more efficiently degraded. Using a genetic screen, we find that reducing endosomal-to-lysosomal trafficking, controlled by the homotypic fusion and vacuole protein sorting (HOPS) complex, rescued the neurotransmission and neurodegeneration defects in sky mutants. Consistently, synaptic vesicle proteins were older in HOPS complex mutants, and these mutants also showed reduced neurotransmission. Our findings define a mechanism in which synaptic transmission is facilitated by efficient protein turnover at lysosomes and identify a potential strategy to suppress defects arising from TBC1D24 mutations in humans.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.