Nuclear Envelope Protein MAN1 Regulates the Drosophila Circadian Clock via Period
Nuclear Envelope Protein MAN1 Regulates the Drosophila Circadian Clock via Period
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核膜蛋白 MAN1 通过周期调节果蝇昼夜节律钟
DOI：
10.1007/s12264-019-00404-6
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发表时间：
2019-12-01
影响因子：
5.6
通讯作者：
Zhang, Luoying
中科院分区：
文献类型：
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作者：
Bu, Bei;He, Weiwei;Zhang, Luoying
几乎所有生物体在大量生物过程中都表现出约 24 小时节律或昼夜节律。这些节律由内源性分子钟驱动，内源性分子钟由一系列转录和翻译反馈环组成。此前，我们已经证明内核膜蛋白 MAN1 调节果蝇的时钟，从而调节果蝇的运动节律，但其机制仍不清楚。在这里，我们进一步证实了之前的发现，发现敲低成年果蝇起搏神经元中的MAN1足以延长运动节律的周期。分子分析显示，敲低 MAN1 会导致核心时钟基因 period (per) 的 mRNA 和蛋白质水平降低，可能是通过减少其转录来实现的。 per 的过表达挽救了 MAN1 缺陷引起的长周期表型，而 per 突变对 MAN1 具有上位效应，表明 MAN1 通过靶向 per 来设定时钟的节奏。
Almost all organisms exhibit ~24-h rhythms, or circadian rhythms, in a plentitude of biological processes. These rhythms are driven by endogenous molecular clocks consisting of a series of transcriptional and translational feedback loops. Previously, we have shown that the inner nuclear membrane protein MAN1 regulates this clock and thus the locomotor rhythm in flies, but the mechanism remains unclear. Here, we further confirmed the previous findings and found that knocking down MAN1 in the pacemaker neurons of adult flies is sufficient to lengthen the period of the locomotor rhythm. Molecular analysis revealed that knocking down MAN1 led to reduced mRNA and protein levels of the core clock gene period (per), likely by reducing its transcription. Over-expressing per rescued the long period phenotype caused by MAN1 deficiency whereas per mutation had an epistatic effect on MAN1, indicating that MAN1 sets the pace of the clock by targeting per.