Sleep-wake cycles drive daily dynamics of synaptic phosphorylation

Research output: Contribution to journalJournal articleResearchpeer-review

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

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.

Original languageEnglish
Article numbereaav3617
JournalScience (New York, N.Y.)
Volume366
Issue number6462
ISSN0036-8075
DOIs
Publication statusPublished - 2019

ID: 229855784