Neuronal proteome dynamics during homeostatic scaling.

Homeostatic scaling adjusts synaptic strength in response to persistent changes in neuronal network activity. This compensatory mechanism requires proteome remodeling accomplished via regulation of protein synthesis as well as degradation, but the global patterns of proteome remodeling and the underlying dynamics of individual proteins remain elusive. Here we used dynamic SILAC labeling in cultured hippocampal cells to identify proteins involved in homeostatic up- or down-scaling and to quantify their changes in synthesis and degradation as well as resulting changes in protein abundance or turnover. Our data demonstrate that a large fraction of the neuronal proteome is remodeled during homeostatic scaling. Most proteins were down-regulated by decreased synthesis or up-regulated by decreased degradation. Comparably fewer proteins showed increased synthesis or degradation rates. More than half of the quantified synaptic proteins were regulated, including pre- as well as postsynaptic proteins with diverse molecular functions.