論文 - 詳細
| RRC ID | 54456 |
|---|---|
| 著者 | Bourouis M, Mondin M, Dussert A, Leopold P. |
| タイトル | Control of basal autophagy rate by vacuolar peduncle. |
| ジャーナル | PLoS One |
| Abstract |
Basal autophagy is as a compressive catabolic mechanism engaged in the breakdown of damaged macromolecules and organelles leading to the recycling of elementary nutrients. Thought essential to cellular refreshing, little is known about the origin of a constitutional rate of basal autophagy. Here, we found that loss of Drosophila vacuolar peduncle (vap), a presumed GAP enzyme, is associated with enhanced basal autophagy rate and physiological alterations resulting in a wasteful cell energy balance, a hallmark of overactive autophagy. By contrast, starvation-induced autophagy was disrupted in vap mutant conditions, leading to a block of maturation into autolysosomes. This phenotype stem for exacerbated biogenesis of PI(3)P-dependent endomembranes, including autophagosome membranes and ectopic fusions of vesicles. These findings shed new light on the neurodegenerative phenotype found associated to mutant vap adult brains in a former study. A partner of Vap, Sprint (Spri), acting as an endocytic GEF for Rab5, had the converse effect of leading to a reduction in PI(3)P-dependent endomembrane formation in mutants. Spri was conditional to normal basal autophagy and instrumental to the starvation-sensitivity phenotype specific of vap. Rab5 activity itself was essential for PI(3)P and for pre-autophagosome structures formation. We propose that Vap/Spri complexes promote a cell surface-derived flow of endocytic Rab5-containing vesicles, the traffic of which is crucial for the implementation of a basal autophagy rate. |
| 巻・号 | 14(2) |
| ページ | e0209759 |
| 公開日 | 2019-2-8 |
| DOI | 10.1371/journal.pone.0209759 |
| PII | PONE-D-18-18762 |
| PMID | 30735514 |
| PMC | PMC6368412 |
| MeSH | Animals Autophagosomes / metabolism Autophagy* Carrier Proteins / metabolism Drosophila / cytology* Drosophila / metabolism Drosophila Proteins / metabolism Female GTPase-Activating Proteins / metabolism Gene Deletion Guanine Nucleotide Exchange Factors Male Phosphatidylinositol Phosphates / metabolism Protein Transport RNA Interference rab5 GTP-Binding Proteins / metabolism |
| IF | 2.776 |
| 引用数 | 0 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ショウジョウバエ | |