Sleep-wake cycles drive daily dynamics of synaptic phosphorylation
Sleep-wake cycles drive daily dynamics of synaptic phosphorylation
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DOI：
10.1126/science.aav3617
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发表时间：
2019-10-11
期刊：
影响因子：
56.9
通讯作者：
Robles, Maria S.
中科院分区：
文献类型：
--
作者：
Bruening, Franziska;Noya, Sara B.;Robles, Maria S.
生物钟通过调节转录、蛋白质丰度和功能来驱动包括睡眠-觉醒周期在内的日常生理变化。昼夜节律的磷酸化控制着外周器官的细胞过程，但对其在脑功能和突触活动中的作用知之甚少。我们将先进的定量磷酸蛋白质组学应用于24小时内分离的小鼠前脑突触神经体，准确地定量了近8000个磷酸肽。一半的突触磷蛋白，包括大量的激酶，具有大幅度的节律，在静息-活动和活动-静息转变时达到峰值。生物信息学分析揭示了突触功能的全球时间控制，包括突触传递、细胞骨架重组和兴奋性/抑制性平衡。睡眠剥夺消除了突触神经体98%的所有磷酸化周期，这表明睡眠-觉醒周期而不是昼夜信号是突触磷酸化的主要驱动因素，对睡眠和醒来的压力都有反应。
The circadian clock drives daily changes of physiology, including sleep-wake cycles, through regulation of transcription, protein abundance, and function. Circadian phosphorylation controls cellular processes in peripheral organs, but little is known about its role in brain function and synaptic activity. We applied advanced quantitative phosphoproteomics to mouse forebrain synaptoneurosomes isolated across 24 hours, accurately quantifying almost 8000 phosphopeptides. Half of the synaptic phosphoproteins, including numerous kinases, had large-amplitude rhythms peaking at rest-activity and activity-rest transitions. Bioinformatic analyses revealed global temporal control of synaptic function through phosphorylation, including synaptic transmission, cytoskeleton reorganization, and excitatory/inhibitory balance. Sleep deprivation abolished 98% of all phosphorylation cycles in synaptoneurosomes, indicating that sleep-wake cycles rather than circadian signals are main drivers of synaptic phosphorylation, responding to both sleep and wake pressures.