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A role for casein kinase 2α in the Drosophila circadian clock

机译：酪蛋白激酶2α在果蝇生物钟中的作用

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摘要

Circadian clocks drive rhythmic behaviour in animals and are regulated by transcriptional feedback loops. For example, the Drosophila proteins Clock (Clk) and Cycle (Cyc) activate transcription of period (per) and timeless (tint). Per and Tim then associate, translocate to the nucleus, and repress the activity of Clk and Cyc. However, post-translational modifications are also critical to proper timing. Per and Tim undergo rhythmic changes in phosphorylation, and evidence supports roles for two kinases in this process: Doubletime (Dbt) phosphorylates Per, whereas Shaggy (Sgg) phosphorylates Tim. Yet Sgg and Dbt often require a phosphoserine in their target site, and analysis of Per phosphorylation in dbt mutants suggests a role for other kinases. Here we show that the catalytic subunit of Drosophila casein kinase 2 (CK2α) is expressed predominantly in the cytoplasm of key circadian pacemaker neurons. CK2α mutant flies show lengthened circadian period, decreased CK2 activity, and delayed nuclear entry of Per. These effects are probably direct, as CK2α specifically phosphorylates Per in vitro. We propose that CK2 is an evolutionary link between the divergent circadian systems of animals, plants and fungi.
机译：昼夜节律时钟驱动动物的节律行为，并受转录反馈回路调节。例如，果蝇蛋白Clock（Clk）和Cycle（Cyc）激活周期（per）和永恒（tint）的转录。然后，Per和Tim缔合，移位至细胞核，并抑制Clk和Cyc的活性。但是，翻译后修饰对于适当的时机也至关重要。 Per和Tim的磷酸化过程发生了规律性变化，证据支持该过程中两种激酶的作用：Doubletime（Dbt）使Per磷酸化，而Shaggy（Sgg）使Tim磷酸化。然而，Sgg和Dbt通常在其靶位点需要磷酸丝氨酸，而对dbt突变体中Per磷酸化的分析表明其他激酶也有作用。在这里，我们显示果蝇酪蛋白激酶2（CK2α）的催化亚基主要在关键昼夜节律起搏器神经元的细胞质中表达。 CK2α突变体果蝇的昼夜节律周期延长，CK2活性降低，Per的核进入延迟。这些作用可能是直接的，因为CK2α在体外特异性磷酸化。我们建议CK2是动植物，真菌和真菌的昼夜节律系统之间的进化联系。

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