Functional analysis of calcineurin, a sleep-related gene in the fruit fly, Drosophila melanogaster

我们最近报道了钙调磷酸酶（Ca^<2+>/钙调素依赖性蛋白磷酸酶）是果蝇睡眠的重要调节因子（Tomita et al., 2011）。calcalineurin A的14F（CanA-14F）是果蝇中三个calcalineurin催化A亚基基因之一，其泛神经元敲低会导致睡眠缺失，而成人特异性的CanA-14F在所有神经元中的组成活性形式的错误表达会增加睡眠。我们利用GAL4-UAS系统靶向敲除CanA-14F，确定了在睡眠调节中对CanA-14F功能起重要作用的脑神经元。此外，我们发现这些神经元中D1多巴胺受体的敲除显著增加了睡眠。这些结果提示在果蝇睡眠调节中Ca^<2+>-钙调磷酸酶和多巴胺能信号通路之间存在交叉对话。

We recently reported that calcineurin(Ca^<2+>/calmodulin-dependent protein phosphatase) is an important regulator of sleep in Drosophila(Tomita et al., 2011). The pan-neuronal knockdown of Calcineurin A at 14F(CanA-14F), which is one of the three calcineurin catalytic A subunit genes in Drosophila, resulted in sleep loss, while an adult-specific misexpression of a constitutively active form of CanA-14F in all neurons increased sleep. We identified brain neurons important for the function of CanA-14F in sleep regulation by targeted CanA-14F knockdown using the GAL4-UAS system. Moreover, we found that knockdown of D1 dopamine receptor in these neurons significantly increased sleep. These results suggest a cross-talk between Ca^<2+>-calcineurin and dopaminergic signaling pathways in Drosophila sleep regulation.