論文 - 詳細
| RRC ID | 47430 |
|---|---|
| 著者 | Danielsen ET, Moeller ME, Yamanaka N, Ou Q, Laursen JM, Soenderholm C, Zhuo R, Phelps B, Tang K, Zeng J, Kondo S, Nielsen CH, Harvald EB, Faergeman NJ, Haley MJ, O'Connor KA, King-Jones K, O'Connor MB, Rewitz KF. |
| タイトル | A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing. |
| ジャーナル | Dev Cell |
| Abstract |
Steroid hormones control important developmental processes and are linked to many diseases. To systematically identify genes and pathways required for steroid production, we performed a Drosophila genome-wide in vivo RNAi screen and identified 1,906 genes with potential roles in steroidogenesis and developmental timing. Here, we use our screen as a resource to identify mechanisms regulating intracellular levels of cholesterol, a substrate for steroidogenesis. We identify a conserved fatty acid elongase that underlies a mechanism that adjusts cholesterol trafficking and steroidogenesis with nutrition and developmental programs. In addition, we demonstrate the existence of an autophagosomal cholesterol mobilization mechanism and show that activation of this system rescues Niemann-Pick type C1 deficiency that causes a disorder characterized by cholesterol accumulation. These cholesterol-trafficking mechanisms are regulated by TOR and feedback signaling that couples steroidogenesis with growth and ensures proper maturation timing. These results reveal genes regulating steroidogenesis during development that likely modulate disease mechanisms. |
| 巻・号 | 37(6) |
| ページ | 558-70 |
| 公開日 | 2016-6-20 |
| DOI | 10.1016/j.devcel.2016.05.015 |
| PII | S1534-5807(16)30328-8 |
| PMID | 27326933 |
| PMC | PMC4918455 |
| MeSH | Acetyltransferases / metabolism Animals Autophagy / genetics Biological Transport / genetics Cholesterol / metabolism Drosophila Proteins / metabolism Drosophila melanogaster / genetics* Ecdysone / metabolism Embryonic Development / genetics* Fatty Acid Elongases Genetic Testing* Genome, Insect* Hormones / biosynthesis* Lipid Metabolism / genetics Phenotype RNA Interference Signal Transduction / genetics Sphingolipids / metabolism Steroids / biosynthesis* Time Factors |
| IF | 10.092 |
| 引用数 | 29 |
| WOS 分野 | DEVELOPMENTAL BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 6 |
| 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 | |