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Science. 2019 Oct 11;366(6462). pii: eaav3617. doi: 10.1126/science.aav3617.

Sleep-wake cycles drive daily dynamics of synaptic phosphorylation.

Author information

1
Institute of Medical Psychology, Faculty of Medicine, LMU Munich, Germany.
2
Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, 82152 Martinsried, Germany.
3
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
4
Computational Systems Biochemistry, Max-Planck Institute of Biochemistry, Martinsried, Germany.
5
Novo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.
6
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland. charo.robles@med.uni-muenchen.de steven.brown@pharma.uzh.ch.
7
Institute of Medical Psychology, Faculty of Medicine, LMU Munich, Germany. charo.robles@med.uni-muenchen.de steven.brown@pharma.uzh.ch.
#
Contributed equally

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.

PMID:
31601740
DOI:
10.1126/science.aav3617

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