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Sleep-wake cycles drive daily dynamics of synaptic phosphorylation

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Brüning,  Franziska
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Rudolph,  Jan D.
Cox, Jürgen / Computational Systems Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society;

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Cox,  Jürgen
Cox, Jürgen / Computational Systems Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society;

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Mann,  Matthias
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Brüning, F., Noya, S. B., Bange, T., Koutsouli, S., Rudolph, J. D., Tyagarajan, S., et al. (2019). Sleep-wake cycles drive daily dynamics of synaptic phosphorylation. SCIENCE, 366(6462): eaav3617, pp. 201. doi:10.1126/science.aav3617.


Cite as: http://hdl.handle.net/21.11116/0000-0005-9911-B
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.