論文 - 詳細
| RRC ID | 57168 |
|---|---|
| 著者 | Kweon SH, Lee J, Lim C, Choe J. |
| タイトル | High-Amplitude Circadian Rhythms in Drosophila Driven by Calcineurin-Mediated Post-translational Control of sarah. |
| ジャーナル | Genetics |
| Abstract |
Post-translational control is a crucial mechanism for circadian timekeeping. Evolutionarily conserved kinases and phosphatases have been implicated in circadian phosphorylation and the degradation of clock-relevant proteins, which sustain high-amplitude rhythms with 24-hr periodicity in animal behaviors and physiology. Here, we report a novel clock function of the heterodimeric Ca2+/calmodulin-dependent phosphatase calcineurin and its regulator sarah (sra) in Drosophila Genomic deletion of the sra locus dampened circadian locomotor activity rhythms in free-running constant dark after entrainment in light-dark cycles. Poor rhythms in sra mutant behaviors were accompanied by lower expression of two oscillating clock proteins, PERIOD (PER) and TIMELESS (TIM), at the post-transcriptional level. RNA interference-mediated sra depletion in circadian pacemaker neurons was sufficient to phenocopy loss-of-function mutation in sra On the other hand, a constitutively active form of the catalytic calcineurin subunit, Pp2B-14DACT, shortened circadian periodicity in locomotor behaviors and phase-advanced PER and TIM rhythms when overexpressed in clock neurons. Heterozygous sra deletion induced behavioral arrhythmicity in Pp2B-14DACT flies, whereas sra overexpression rescued short periods in these animals. Finally, pharmacological inhibition of calcineurin in either wild-type flies or clock-less S2 cells decreased the levels of PER and TIM, likely by facilitating their proteasomal degradation. Taken together, these data suggest that sra negatively regulates calcineurin by cell-autonomously titrating calcineurin-dependent stabilization of PER and TIM proteins, thereby sustaining high-amplitude behavioral rhythms in Drosophila. |
| 巻・号 | 209(3) |
| ページ | 815-828 |
| 公開日 | 2018-7-1 |
| DOI | 10.1534/genetics.118.300808 |
| PII | genetics.118.300808 |
| PMID | 29724861 |
| PMC | PMC6028259 |
| MeSH | Animals Calcineurin / metabolism* Calcium-Binding Proteins Cell Line Circadian Rhythm Drosophila / genetics Drosophila / metabolism Drosophila / physiology* Drosophila Proteins / genetics* Drosophila Proteins / metabolism* Gene Deletion Gene Expression Regulation Intracellular Signaling Peptides and Proteins / genetics* Intracellular Signaling Peptides and Proteins / metabolism Period Circadian Proteins / genetics Period Circadian Proteins / metabolism* Protein Processing, Post-Translational Proteolysis |
| IF | 3.564 |
| 引用数 | 1 |
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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 | 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 |
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