論文 - 詳細
| RRC ID | 69046 |
|---|---|
| 著者 | Lee J, Lim C, Han TH, Andreani T, Moye M, Curran J, Johnson E, Kath WL, Diekman CO, Lear BC, Allada R. |
| タイトル | The E3 ubiquitin ligase adaptor Tango10 links the core circadian clock to neuropeptide and behavioral rhythms. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
Circadian transcriptional timekeepers in pacemaker neurons drive profound daily rhythms in sleep and wake. Here we reveal a molecular pathway that links core transcriptional oscillators to neuronal and behavioral rhythms. Using two independent genetic screens, we identified mutants of Transport and Golgi organization 10 (Tango10) with poor behavioral rhythmicity. Tango10 expression in pacemaker neurons expressing the neuropeptide PIGMENT-DISPERSING FACTOR (PDF) is required for robust rhythms. Loss of Tango10 results in elevated PDF accumulation in nerve terminals even in mutants lacking a functional core clock. TANGO10 protein itself is rhythmically expressed in PDF terminals. Mass spectrometry of TANGO10 complexes reveals interactions with the E3 ubiquitin ligase CULLIN 3 (CUL3). CUL3 depletion phenocopies Tango10 mutant effects on PDF even in the absence of the core clock gene timeless Patch clamp electrophysiology in Tango10 mutant neurons demonstrates elevated spontaneous firing potentially due to reduced voltage-gated Shaker-like potassium currents. We propose that Tango10/Cul3 transduces molecular oscillations from the core clock to neuropeptide release important for behavioral rhythms. |
| 巻・号 | 118(47) |
| 公開日 | 2021-11-23 |
| DOI | 10.1073/pnas.2110767118 |
| PII | 2110767118 |
| PMID | 34799448 |
| PMC | PMC8617488 |
| MeSH | Animals Aryl Hydrocarbon Receptor Nuclear Translocator / genetics Aryl Hydrocarbon Receptor Nuclear Translocator / metabolism Circadian Clocks / physiology* Cullin Proteins / genetics Cullin Proteins / metabolism Drosophila Drosophila Proteins / genetics Drosophila Proteins / metabolism* Neurons / metabolism Neuropeptides / genetics Neuropeptides / metabolism* Proteomics Sleep Ubiquitin-Protein Ligases / metabolism* |
| IF | 9.412 |
| リソース情報 | |
| ショウジョウバエ | 11861R-2 |