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Phosphorylation in synaptic plasticity

ABSTRACT: Homeostatic synaptic scaling is a compensatory mechanism that allows adjustment of the strength of synaptic connections up or down in response to changes in input to maintain global network stability. To characterize the molecular changes on the level of protein modification that contribute to synaptic scaling, we examined changes of the proteome and phosphoproteome in response to activity manipulation. For this purpose, we pharmacologically induced up- or down-scaling in primary cultured cortical neurons for different time spans ranging from minutes (5 min, 15 min) up to one day. Temporal snapshots of the neuronal proteome and phosphoproteome were obtained using high-resolution LC-MS/MS analyses. Our data cover 45,395 phosphorylated peptide species that map to 26,642 unique phosphorylation sites. Activity manipulation elicited significant regulation of 3,382 phosphorylation events on proteins predominantly located at the synaptic compartment or involved in organization of the cytoskeleton. With respect to the temporal regulation, we discovered that phosphomodulation during scaling was not only achieved by time-limited phosphorylation, but for a quarter of initial sites also by persistent regulation. Persistence in phosphorylation was associated with reciprocity in the sign of its regulation, reflecting the two different scaling polarities.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain, Primary Cell, Cell Culture

SUBMITTER: Julian Langer

LAB HEAD: Julian Langer

PROVIDER: PXD021834 | Pride | 2021-08-12

REPOSITORIES: Pride

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