德国慕尼黑大学Maria S. Robles和瑞士苏黎世大学Steven A. Brown等研究人员合作揭示了睡眠-清醒周期引起的突触蛋白质组磷酸化的日常动态。相关论文发表在2019年10月11日出版的《科学》杂志上。

研究人员对在24小时内分离出的小鼠前脑突触神经小体应用了先进的定量磷酸化蛋白质组学，可准确定量近8000种磷酸肽。一半的突触磷酸化蛋白（包括许多激酶）在休息-活动和活动-休息过渡时具有最大振幅的节律。生物信息学分析揭示了通过磷酸化对突触功能的总体时间控制，包括突触传递、细胞骨架重组和兴奋/抑制平衡。

睡眠剥夺消除了突触神经小体中所有磷酸化周期的98％，这表明睡眠-清醒周期而非昼夜节律信号是突触磷酸化的主要驱动因素，并对睡眠和觉醒压力均有反应。

据悉，昼夜节律通过调节转录、蛋白质丰度和功能来驱动生理的日常变化，包括睡眠-清醒周期。昼夜节律性磷酸化调控外围器官中的细胞过程，但对其在脑功能和突触活动中的作用知之甚少。

附：英文原文

Title: Sleep-wake cycles drive daily dynamics of synaptic phosphorylation

Author: Franziska Brüning, Sara B. Noya, Tanja Bange, Stella Koutsouli, Jan D. Rudolph, Shiva K. Tyagarajan, Jürgen Cox, Matthias Mann, Steven A. Brown, Maria S. Robles

Issue&Volume: Volume 366 Issue 6462

Abstract: 

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.

DOI: 10.1126/science.aav3617

Source: https://science.sciencemag.org/content/366/6462/eaav3617