論文 - 詳細
| RRC ID | 5661 |
|---|---|
| 著者 | Chang YY, Neufeld TP. |
| タイトル | An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy regulation. |
| ジャーナル | Mol Biol Cell |
| Abstract |
The TOR kinases are conserved negative regulators of autophagy in response to nutrient conditions, but the signaling mechanisms are poorly understood. Here we describe a complex containing the protein kinase Atg1 and the phosphoprotein Atg13 that functions as a critical component of this regulation in Drosophila. We show that knockout of Atg1 or Atg13 results in a similar, selective defect in autophagy in response to TOR inactivation. Atg1 physically interacts with TOR and Atg13 in vivo, and both Atg1 and Atg13 are phosphorylated in a nutrient-, TOR- and Atg1 kinase-dependent manner. In contrast to yeast, phosphorylation of Atg13 is greatest under autophagic conditions and does not preclude Atg1-Atg13 association. Atg13 stimulates both the autophagic activity of Atg1 and its inhibition of cell growth and TOR signaling, in part by disrupting the normal trafficking of TOR. In contrast to the effects of normal Atg13 levels, increased expression of Atg13 inhibits autophagosome expansion and recruitment of Atg8/LC3, potentially by decreasing the stability of Atg1 and facilitating its inhibitory phosphorylation by TOR. Atg1-Atg13 complexes thus function at multiple levels to mediate and adjust nutrient-dependent autophagic signaling. |
| 巻・号 | 20(7) |
| ページ | 2004-14 |
| 公開日 | 2009-4-1 |
| DOI | 10.1091/mbc.e08-12-1250 |
| PII | E08-12-1250 |
| PMID | 19225150 |
| PMC | PMC2663935 |
| MeSH | Amino Acid Sequence Animals Autophagy* Autophagy-Related Protein-1 Homolog Autophagy-Related Proteins Drosophila Proteins / chemistry Drosophila Proteins / metabolism* Drosophila melanogaster / cytology* Drosophila melanogaster / metabolism* Molecular Sequence Data Mutation Phosphatidylinositol 3-Kinases / metabolism* Phosphorylation Protein Binding Protein Kinases Protein Serine-Threonine Kinases / metabolism* Protein Transport Signal Transduction TOR Serine-Threonine Kinases |
| IF | 3.791 |
| 引用数 | 257 |
| 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 | Clinical guideline |
| 各媒体での言及数の合計 | 1 |
| 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 | |