![]() ![]() In both of these studies, however, average half-lives were obtained using mixed cell populations including multiple neuronal and glial cell types. Another study used in vitro metabolic labeling of primary cortical cultures to measure relatively shorter half-lives for 2802 brain proteins (average half-life =~5 days ( Cohen et al., 2013)). (2010) used in vivo metabolic 15N-labelling and the subsequent mass spectrometric analysis of whole brain homogenates to derive the turnover rates for 1010 proteins (average half-life =~9 days) in the mouse brain. The turnover of brain proteins has been measured both in vivo and in vitro. During homeostatic scaling of cultured hippocampal neurons, for example, specific sets of proteins show increased or decreased protein synthesis associated with the up- or downscaling of synapses ( Schanzenbächer et al., 2018 Schanzenbächer et al., 2016). In addition, several forms of synaptic plasticity studied in vitro also require protein synthesis and protein degradation ( Ehlers, 2003 Kang and Schuman, 1996 Rosenberg et al., 2014 Schanzenbächer et al., 2016). In the brain, proteome remodeling using protein synthesis and degradation is required for learning and memory formation ( Sutton and Schuman, 2006). Turnover rates have likely been optimized during evolution such that individual proteins possess a life time that represents the balance between energy-saving stability and dynamic flexibility. In addition, continuous protein turnover is required and exploited to enable cells to dynamically adjust their proteome according to internal and external perturbations and signals. Protein turnover allows for the removal of damaged proteins and their replacement by new proteins. Under steady-state conditions, proteins are continuously turned over ( Boisvert et al., 2012 Cambridge et al., 2011 Cohen et al., 2013 Price et al., 2010). Protein turnover, measured in cells, is the net result of protein synthesis and degradation. Proteins, the fundamental units of all cells, exhibit dynamics in their expression levels in response to intracellular and extracellular signals. Our results demonstrate that both the cell-type of origin as well as the nature of the extracellular environment have potent influences on protein turnover. ![]() The presence of glia sped up or slowed down the turnover of neuronal proteins. Proteins in glia possessed shorter half-lives than the same proteins in neurons. Half-lives also correlate with protein functions and the dynamics of the complexes they are incorporated in. ![]() In contrast to synaptic proteins, membrane proteins were relatively shorter-lived and mitochondrial proteins were longer-lived compared to the population. We used dynamic SILAC to determine half-lives of over 5100 proteins in rat primary hippocampal cultures as well as in neuron-enriched and glia-enriched cultures ranging from 20 days. ![]() Proteins can show different turnover rates in different tissue, but little is known about protein turnover in different brain cell types. Regulation of protein turnover allows cells to react to their environment and maintain homeostasis. ![]()
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