Daytime CLOCK Dephosphorylation Is Controlled by STRIPAK Complexes in Drosophila
Daytime CLOCK Dephosphorylation Is Controlled by STRIPAK Complexes in Drosophila
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DOI：
10.1016/j.celrep.2015.04.033
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发表时间：
2015-05-26
期刊：
影响因子：
8.8
通讯作者：
Rouyer, Francois
中科院分区：
文献类型：
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作者：
Andreazza, Simonetta;Bouleau, Sylvina;Rouyer, Francois
在果蝇昼夜节律振荡器中，时钟/周期复合物在晚上激活周期（per）和无时间（tim）的转录。然后PER和TIM蛋白在夜间抑制时钟（CLK）活动。振荡器的速度取决于翻译后调节，其影响转录环的正向和负向组分。CLK蛋白在早上高度磷酸化且无活性，而低磷酸化的活性形式存在于晚上。这一关键的去磷酸化步骤是如何介导的尚不清楚。在这里，我们表明，两个组成部分的STRIPAK复合物，CKA调节亚基的PP 2A磷酸酶和其相互作用的蛋白质STRIP，促进CLK去磷酸化在白天。相比之下，WDB调节PP 2A亚基稳定CLK而不影响其磷酸化状态。抑制PP 2A催化亚基和CKA下调影响白天CLK类似，这表明STRIPAK复合物是产生转录活性低磷酸化CLK的主要PP 2A参与者。
In the Drosophila circadian oscillator, the CLOCK/CYCLE complex activates transcription of period (per) and timeless (tim) in the evening. PER and TIM proteins then repress CLOCK (CLK) activity during the night. The pace of the oscillator depends upon post-translational regulation that affects both positive and negative components of the transcriptional loop. CLK protein is highly phosphorylated and inactive in the morning, whereas hypophosphorylated active forms are present in the evening. How this critical dephosphorylation step is mediated is unclear. We show here that two components of the STRIPAK complex, the CKA regulatory subunit of the PP2A phosphatase and its interacting protein STRIP, promote CLK dephosphorylation during the daytime. In contrast, the WDB regulatory PP2A subunit stabilizes CLK without affecting its phosphorylation state. Inhibition of the PP2A catalytic subunit and CKA downregulation affect daytime CLK similarly, suggesting that STRIPAK complexes are the main PP2A players in producing transcriptionally active hypophosphorylated CLK.