論文 - 詳細
| RRC ID | 33069 |
|---|---|
| 著者 | Grima B, Dognon A, Lamouroux A, Chélot E, Rouyer F. |
| タイトル | CULLIN-3 controls TIMELESS oscillations in the Drosophila circadian clock. |
| ジャーナル | PLoS Biol |
| Abstract |
Eukaryotic circadian clocks rely on transcriptional feedback loops. In Drosophila, the PERIOD (PER) and TIMELESS (TIM) proteins accumulate during the night, inhibit the activity of the CLOCK (CLK)/CYCLE (CYC) transcriptional complex, and are degraded in the early morning. The control of PER and TIM oscillations largely depends on post-translational mechanisms. They involve both light-dependent and light-independent pathways that rely on the phosphorylation, ubiquitination, and proteasomal degradation of the clock proteins. SLMB, which is part of a CULLIN-1-based E3 ubiquitin ligase complex, is required for the circadian degradation of phosphorylated PER. We show here that CULLIN-3 (CUL-3) is required for the circadian control of PER and TIM oscillations. Expression of either Cul-3 RNAi or dominant negative forms of CUL-3 in the clock neurons alters locomotor behavior and dampens PER and TIM oscillations in light-dark cycles. In constant conditions, CUL-3 deregulation induces behavioral arrhythmicity and rapidly abolishes TIM cycling, with slower effects on PER. CUL-3 affects TIM accumulation more strongly in the absence of PER and forms protein complexes with hypo-phosphorylated TIM. In contrast, SLMB affects TIM more strongly in the presence of PER and preferentially associates with phosphorylated TIM. CUL-3 and SLMB show additive effects on TIM and PER, suggesting different roles for the two ubiquitination complexes on PER and TIM cycling. This work thus shows that CUL-3 is a new component of the Drosophila clock, which plays an important role in the control of TIM oscillations. |
| 巻・号 | 10(8) |
| ページ | e1001367 |
| 公開日 | 2012-8-7 |
| DOI | 10.1371/journal.pbio.1001367 |
| PII | PBIOLOGY-D-12-01645 |
| PMID | 22879814 |
| PMC | PMC3413713 |
| MeSH | Animals Behavior, Animal / physiology* Blotting, Western Circadian Clocks* Cullin Proteins / genetics Cullin Proteins / metabolism* Drosophila / genetics Drosophila / metabolism* Drosophila / physiology Drosophila Proteins / genetics Drosophila Proteins / metabolism* Gene Expression Regulation Locomotion Multiprotein Complexes / metabolism Neurons / metabolism Period Circadian Proteins / metabolism Phosphorylation Protein Stability Proteolysis RNA Interference RNA, Messenger / analysis RNA, Messenger / metabolism Ubiquitination |
| IF | 7.076 |
| 引用数 | 30 |
| WOS 分野 | BIOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 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 | 11861R-1 11861R-2 |