Abstract
Protein turnover, the net result of protein synthesis and degradation, enables cells to remodel their proteomes in response to internal and external cues. Previously, we analyzed protein turnover rates in cultured brain cells under basal neuronal activity and found that protein turnover is influenced by subcellular localization, protein function, complex association, cell type of origin, and by the cellular environment (Dörrbaum et al., 2018). Here, we advanced our experimental approach to quantify changes in protein synthesis and degradation, as well as the resulting changes in protein turnover or abundance in rat primary hippocampal cultures during homeostatic scaling. Our data demonstrate that a large fraction of the neuronal proteome shows changes in protein synthesis and/or degradation during homeostatic up- and down-scaling. More than half of the quantified synaptic proteins were regulated, including pre- as well as postsynaptic proteins with diverse molecular functions.
Highlights
Long-lasting changes in synaptic strength, which are a basis for learning and memory formation, require de-novo protein synthesis as well as the degradation of existing proteins (Cajigas et al, 2010; Hegde, 2017; Jarome and Helmstetter, 2013; Tai and Schuman, 2008)
Among the proteins that were up-regulated by decreased degradation, we found an over-representation of proteins involved in translation, as well as proteins involved in proteolysis
Among the proteins that were down-regulated by decreased synthesis, we found an over-representation of many synaptic terms, including ‘GABA-ergic synapse’ and ‘glutamatergic synapse’
Summary
Long-lasting changes in synaptic strength, which are a basis for learning and memory formation, require de-novo protein synthesis as well as the degradation of existing proteins (Cajigas et al, 2010; Hegde, 2017; Jarome and Helmstetter, 2013; Tai and Schuman, 2008). Several forms of synaptic plasticity studied in vitro, including homeostatic scaling, require protein synthesis and degradation (Ehlers, 2003; Kang and Schuman, 1996; Rosenberg et al, 2014; Schanzenbacher et al, 2016). Homeostatic scaling cannot be evoked in the presence of protein synthesis inhibitors or proteasome inhibitors (Ehlers, 2003; Schanzenbacher et al, 2016)
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