主题：In situ Protein Copy Counting at Brain Synapses
An individual neuron hosts about 10000 synapses in its expansive dendritic and axonal arbor. To support parallel information processing, major cell-biological machineries are decentralized to individual synapses, including the machinery for protein turnover. To measure the local protein synthesis and -degradation capacity, we counted the copy numbers of dendritic ribosomes and proteasomes via single-molecule localization microscopy. In combination with metabolic labeling and single-spine plasticity induction, we reveal the spatial specificity of activity-induced local protein synthesis. The single-molecule resolution further affords quantitative mapping of different proteasome assembly states and reveals a surprising abundance of free regulatory particles 19S in dendrites. These 'solitary' dendritic proteasome regulatory particles regulate synaptic transmission via atypical ubiquitin signaling of key synaptic proteins such as AMPA receptors. As such, synapses can use alternative machine formats to carry out different functions, akin to protein ‘moonlighting’.
Associate Professor,Department of Molecular Biology and Genetics - Neurobiology,Aarhus University
Aarhus C, Denmark.
2018-2022 EMBO and HFSP postdoctoral fellow, Erin Schuman lab, Max Planck Institute for Brain Research, Germany
2018 Trainee, Neurobiology course, Marine Biological Laboratory in Woods Hole, USA
2016-2018 Predoctoral visiting scholar, Northwestern University, USA
2013-2018 PhD student, William R. Dichtel lab, Cornell University, USA