Reassessing the involvement of the CREB pathway in the circadian clock of Drosophila melanogaster

Anna Katharina Eick, Maite Ogueta, Ralf Stanewsky
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Abstract

Circadian clocks are ubiquitous in almost all organisms on Earth and many key genes are highly conserved among species. In the mammalian suprachiasmatic nucleus, the cAMP response element binding protein (CREB) pathway is known to play a crucial role in conveying light-input to the transcription of clock genes. The fruit fly Drosophila melanogaster also expresses two Creb proteins, CrebA and CrebB, which have been associated with the circadian clock. For example, Drosophila Creb has been suggested to constitute a molecular link between neuronal excitability and clock gene transcription. In this study we subjected flies with clock cell specific CrebA or CrebB mutations to circadian behavioral and bioluminescence assays. Surprisingly, we found that neither loss of CrebA or CrebB did affect free-running locomotor behavior, rhythmic period oscillations in clock neurons, or light-dependent synchronization. In conclusion our findings question the conserved circadian role of the Creb pathway in Drosophila and encourage further studies to elucidate its potential function within insect circadian clocks.

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重新评估CREB通路在黑腹果蝇生物钟中的作用
生物钟在地球上几乎所有生物中都无处不在,许多关键基因在物种之间高度保守。在哺乳动物视交叉上核中,cAMP反应元件结合蛋白(CREB)通路在将光输入传递给时钟基因的转录过程中起着至关重要的作用。果蝇也表达两种Creb蛋白,CrebA和CrebB,这两种蛋白与生物钟有关。例如,果蝇Creb被认为是神经元兴奋性和时钟基因转录之间的分子联系。在这项研究中,我们对具有时钟细胞特异性CrebA或CrebB突变的果蝇进行了昼夜行为和生物发光测定。令人惊讶的是,我们发现CrebA或CrebB的缺失都不会影响自由奔跑的运动行为、时钟神经元的节律周期振荡或光依赖同步。总之,我们的研究结果质疑了Creb通路在果蝇中保守的昼夜节律作用,并鼓励进一步研究阐明其在昆虫生物钟中的潜在功能。
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