論文 - 詳細
| RRC ID | 36009 |
|---|---|
| 著者 | Klinman E, Holzbaur EL. |
| タイトル | Stress-Induced CDK5 Activation Disrupts Axonal Transport via Lis1/Ndel1/Dynein. |
| ジャーナル | Cell Rep |
| Abstract |
Axonal transport is essential for neuronal function, and defects in transport are associated with multiple neurodegenerative diseases. Aberrant cyclin-dependent kinase 5 (CDK5) activity, driven by the stress-induced activator p25, also is observed in these diseases. Here we show that elevated CDK5 activity increases the frequency of nonprocessive events for a range of organelles, including lysosomes, autophagosomes, mitochondria, and signaling endosomes. Transport disruption induced by aberrant CDK5 activation depends on the Lis1/Ndel1 complex, which directly regulates dynein activity. CDK5 phosphorylation of Ndel1 favors a high affinity Lis1/Ndel/dynein complex that blocks the ATP-dependent release of dynein from microtubules, inhibiting processive motility of dynein-driven cargo. Similar transport defects observed in neurons from a mouse model of amyotrophic lateral sclerosis are rescued by CDK5 inhibition. Together, these studies identify CDK5 as a Lis1/Ndel1-dependent regulator of transport in stressed neurons, and suggest that dysregulated CDK5 activity contributes to the transport deficits observed during neurodegeneration. |
| 巻・号 | 12(3) |
| ページ | 462-73 |
| 公開日 | 2015-7-21 |
| DOI | 10.1016/j.celrep.2015.06.032 |
| PII | S2211-1247(15)00644-0 |
| PMID | 26166569 |
| PMC | PMC4532378 |
| MeSH | 1-Alkyl-2-acetylglycerophosphocholine Esterase / genetics 1-Alkyl-2-acetylglycerophosphocholine Esterase / metabolism* Amyotrophic Lateral Sclerosis / metabolism Animals Axonal Transport / physiology* Carrier Proteins / genetics Carrier Proteins / metabolism* Cyclin-Dependent Kinase 5 / genetics Cyclin-Dependent Kinase 5 / metabolism* Disease Models, Animal Dyneins / metabolism* Endosomes / metabolism HeLa Cells Humans Lysosomes / metabolism Mice Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / metabolism* Neurons / metabolism |
| IF | 8.109 |
| 引用数 | 34 |
| WOS 分野 | CELL BIOLOGY |
| 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 | 9 |
| 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 | RBRC00806 |