Reference - Detail
| RRC ID | 87609 |
|---|---|
| Author | Hsu CH, Li YJ, Guo TN, Tzou FY, Hong CL, Lin CH, Huang SY, Chan CC. |
| Title | The cell autonomous and non-autonomous functions of Rab27 in longevity and neuroprotection in Drosophila. |
| Journal | Autophagy |
| Abstract |
Autophagic decline accompanies age and causes a deterioration in proteostasis, rendering neuronal demise. Rab27 functions as a vesicle regulator for macroautophagic/autophagic degradation and exocytosis. Loss of Drosophila Rab27 in αβp brain neurons enhances longevity, underscoring its neuronal role and systemic effect. To understand the underlying mechanisms, we characterized the cell autonomous and non-autonomous functions of Rab27. Rab27 expression increased in midlife, providing a temporal manipulation window. Depleting Rab27 at that timepoint activated autophagy and sustained neuronal maintenance. At the organismic level, Egfr (Epidermal growth factor receptor) ligand was reduced and Akt kinase underphosphorylated in the Rab27 KO fly body, indicating a widespread signaling cascade. Finally, Rab27 KO ameliorates the neurotoxicity in a fly α-synucleinopathy model. Altogether, our results highlight a neuronal autophagy regulator exerting systemic effects that are crucial for neuronal maintenance and improving longevity.Abbreviation: Atg autophagy-related genes;EGF: epidermal growth factor; Egfr: Epidermal growth factor receptor;EGFR: epidermal growth factor receptor; foxo: forkhead box, sub-groupO; mTor: mechanistic target of rapamycin; MTOR: mechanistic target ofrapamycin; spi: spitz. |
| Volume | 21(12) |
| Pages | 2809-2825 |
| Published | 2025-12-1 |
| DOI | 10.1080/15548627.2025.2541384 |
| PMID | 40765016 |
| PMC | PMC12758210 |
| MeSH | Animals Autophagy / genetics Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster* / metabolism ErbB Receptors / metabolism Longevity* / genetics Longevity* / physiology Neurons / metabolism Neuroprotection* Proto-Oncogene Proteins c-akt / metabolism Signal Transduction TOR Serine-Threonine Kinases / metabolism alpha-Synuclein / metabolism rab GTP-Binding Proteins* / metabolism rab27 GTP-Binding Proteins* / metabolism |
| IF | 9.77 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Bluesky |
| Total number of mentions | 7 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Drosophila | |