A role for CK2 in the Drosophila circadian oscillator
A role for CK2 in the Drosophila circadian oscillator
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DOI：
10.1038/nn1007
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发表时间：
2003-03-01
影响因子：
25
通讯作者：
Jackson, FR
中科院分区：
文献类型：
--
作者：
Akten, B;Jauch, E;Jackson, FR
时钟蛋白的翻译后修饰对于昼夜节律振荡器的功能至关重要。通过对黑腹果蝇昼夜节律时钟突变体 Andante（其昼夜节律周期异常长）进行遗传分析，我们发现酪蛋白激酶 2 (CK2) 在决定经期长度方面发挥着作用。 Andante 是编码 CK2 β 亚基的基因的突变，预计会扰乱 CK2β 亚基二聚化。它与β亚基水平降低有关，表明α：β关联和四聚体α2：β2全酶的产生存在缺陷。与对时钟机制的直接作用一致，我们表明 CK2beta 位于时钟神经元内，并且时钟蛋白 period (Per) 和 Timeless (Tim) 在 Andante 突变体中积累到异常高的水平。此外，Andante 中 Per 和 Tim 的核转位被延迟，这种缺陷解释了突变体的长周期表型。这些结果表明分子振荡器中存在 CK2 依赖性磷酸化功能。
The posttranslational modification of clock proteins is critical for the function of circadian oscillators. By genetic analysis of a Drosophila melanogaster circadian clock mutant known as Andante, which has abnormally long circadian periods, we show that casein kinase 2 (CK2) has a role in determining period length. Andante is a mutation of the gene encoding the beta subunit of CK2 and is predicted to perturb CK2beta subunit dimerization. It is associated with reduced beta subunit levels, indicative of a defect in alpha:beta association and production of the tetrameric alpha2:beta2 holoenzyme. Consistent with a direct action on the clock mechanism, we show that CK2beta is localized within clock neurons and that the clock proteins Period (Per) and Timeless (Tim) accumulate to abnormally high levels in the Andante mutant. Furthermore, the nuclear translocation of Per and Tim is delayed in Andante, and this defect accounts for the long-period phenotype of the mutant. These results suggest a function for CK2-dependent phosphorylation in the molecular oscillator.