Proteomics

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Sleep-wake cycles drive daily dynamics of synaptic phosphorylation


ABSTRACT: The circadian clock drives daily changes of physiology, including sleep-wake cycles, by regulating 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 24h, accurately quantifying almost 8,000 phosphopeptides. Remarkably, 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 via phosphorylation, including synaptic transmission, cytoskeleton reorganization and excitatory/inhibitory balance. Remarkably, 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Mario Oroshi  

LAB HEAD: Maria S Robles

PROVIDER: PXD010697 | Pride | 2019-10-14

REPOSITORIES: Pride

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Publications

The forebrain synaptic transcriptome is organized by clocks but its proteome is driven by sleep.

Noya Sara B SB   Colameo David D   Brüning Franziska F   Spinnler Andrea A   Mircsof Dennis D   Opitz Lennart L   Mann Matthias M   Tyagarajan Shiva K SK   Robles Maria S MS   Brown Steven A SA  

Science (New York, N.Y.) 20191001 6462


Neurons have adapted mechanisms to traffic RNA and protein into distant dendritic and axonal arbors. Taking a biochemical approach, we reveal that forebrain synaptic transcript accumulation shows overwhelmingly daily rhythms, with two-thirds of synaptic transcripts showing time-of-day-dependent abundance independent of oscillations in the soma. These transcripts formed two sharp temporal and functional clusters, with transcripts preceding dawn related to metabolism and translation and those anti  ...[more]

Publication: 1/2

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