Disentangling protein synthesis, trafficking and degradation across the mouse brain
1 Institute of Experimental Epileptology and Cognition Research, University of Bonn Medical Center, Bonn, Germany
2 HHMI Janelia Research Campus, Ashburn, VA, USA
Establishing and maintaining dynamic synaptic connections is a key principle of neuronal computations. Tight control of protein levels across the dendrites is crucial to ensure synaptic function. Changes in the synaptic proteome have been associated with compromised synaptic function and in severe cases disease phenotypes. Among the major factors regulating protein levels are protein synthesis, trafficking and degradation. While there is substantial literature on protein synthesis, the role of trafficking and degradation in the dynamic control of synaptic copy numbers is less well understood. Moreover, it is unclear how these processes are coordinated spatially and temporally within single neurons and across different cell types. To elucidate this question, we combined data on the brain-wide turnover of the protein PSD-95 in the mouse brain (1) with a mathematical model. PSD-95 is a postsynaptic structural protein closely linked to synaptic strength. Our approach allows us to explain the half-life profile of the PSD-95 distribution in dendrites and sheds light on how it is shaped by the individual contributions of protein synthesis, trafficking and degradation. In summray, we provide a new perspective on how intracellular dynamics and turnover shape the molecular basis of synaptic plasticity. (1) Mohar B. et al., Brain-wide measurement of protein turnover with high spatial and temporal resolution. biorxiv (2022), doi.org/10.1101/2022.11.12.516226