論文 - 詳細
| RRC ID | 88448 |
|---|---|
| 著者 | Gu Q, Jiao S, Duan K, Wang YX, Petralia RS, Li Z. |
| タイトル | The BAD-BAX-Caspase-3 Cascade Modulates Synaptic Vesicle Pools via Autophagy. |
| ジャーナル | J Neurosci |
| Abstract |
The BAD-BAX-caspase-3 cascade is a canonical apoptosis pathway. Macroautophagy ("autophagy" hereinafter) is a process by which organelles and aggregated proteins are delivered to lysosomes for degradation. Here, we report a new function of the BAD-BAX-caspase-3 cascade and autophagy in the control of synaptic vesicle pools. We found that, in hippocampal neurons of male mice, the BAD-BAX-caspase-3 pathway regulates autophagy, which in turn limits the size of synaptic vesicle pools and influences the kinetics of activity-induced depletion and recovery of synaptic vesicle pools. Moreover, the caspase-autophagy pathway is engaged by fear conditioning to facilitate associative fear learning and memory. This work identifies a new mechanism for controlling synaptic vesicle pools, and a novel, nonapoptotic, presynaptic function of the BAD-BAX-caspase-3 cascade.SIGNIFICANCE STATEMENT Despite the importance of synaptic vesicles for neurons, little is known about how the size of synaptic vesicle pools is maintained under basal conditions and regulated by neural activity. This study identifies a new mechanism for the control of synaptic vesicle pools, and a new, nonapoptotic function of the BAD-BAX-caspase-3 pathway in presynaptic terminals. Additionally, it indicates that autophagy is not only a homeostatic mechanism to maintain the integrity of cells and tissues, but also a process engaged by neural activity to regulate synaptic vesicle pools for optimal synaptic responses, learning, and memory. |
| 巻・号 | 41(6) |
| ページ | 1174-1190 |
| 公開日 | 2021-2-10 |
| DOI | 10.1523/JNEUROSCI.0969-20.2020 |
| PII | JNEUROSCI.0969-20.2020 |
| PMID | 33303681 |
| PMC | PMC7888220 |
| MeSH | Animals Autophagy / physiology* Caspase 3 / deficiency* Caspase 3 / genetics Cells, Cultured HEK293 Cells Humans Male Mice Mice, Knockout Molecular Imaging / methods Organ Culture Techniques Signal Transduction / physiology* Synaptic Vesicles / genetics Synaptic Vesicles / metabolism* Synaptic Vesicles / ultrastructure bcl-2-Associated X Protein / deficiency* bcl-2-Associated X Protein / genetics bcl-Associated Death Protein / deficiency* bcl-Associated Death Protein / genetics |
| IF | 5.674 |
| 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 | 2 |
| 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 | |
| 実験動物マウス | RBRC02759 RBRC02975 |