Crosstalk between calcineurin and dopaminergic signaling in Drosophila sleep regulation

我们之前已经报道了钙调神经磷酸酶(钙/钙调蛋白依赖的蛋白磷酸酶)调节果蝇的睡眠。泛神经元钙调神经磷酸酶基因敲除会显著减少睡眠。然而，我们无法确定通过钙调神经磷酸酶基因敲除而导致睡眠减少的特定大脑区域，这表明大脑中普遍存在的钙调神经磷酸酶活动参与了睡眠调节。我们发现，与对照果蝇相比，钙调神经磷酸酶RNAi果蝇的反弹睡眠时间显著增加。因此，我们假设钙调神经磷酸酶在睡眠调节的突触动态平衡假说中起作用。为了了解钙调神经磷酸酶在突触内稳态假说中的功能，我们研究了神经元中线粒体动力学与睡眠之间的关系。尽管线粒体转运的泛神经元损伤显著增加了睡眠，但钙调神经磷酸酶基因敲除并不影响昼夜节律时钟神经元中线粒体的分布。

We have previously reported that calcineurin (Ca2+/calmodulin-dependent protein phosphatase) regulates sleep in Drosophila. Pan-neuronal calcineurin knockdown significantly decreases sleep. However, we could not identify a specific brain region important for reducing sleep by calcineurin knockdown, suggesting that ubiquitous calcineurin activity in the brain is involved in sleep regulation. We found that the amount of rebound sleep was significantly increased in calcineurin RNAi flies compared to control flies. Thus, we hypothesize that calcineurin plays a role in the synaptic homeostasis hypothesis of sleep regulation. To understand calcineurin function in the synaptic homeostasis hypothesis, we examined the relationship between mitochondrial dynamics in neurons and sleep. Although pan-neuronal impairment of mitochondrial transport significantly increased sleep, mitochondrial distribution in circadian clock neurons was not affected by calcineurin knockout.