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Updated: Jul 29, 2025

Quantifying Subcellular Ubiquitin-proteasome Activity in the Rodent Brain
Published on: May 21, 2019
An abundance of free regulatory (19S) proteasome particles regulates neuronal synapses
Chao Sun1, Kristina Desch1, Belquis Nassim-Assir1
1Max Planck Institute for Brain Research, 60438 Frankfurt am Main, Germany.
Abstract:
The proteasome, the major protein-degradation machine in cells, regulates neuronal synapses and long-term information storage. Here, using super-resolution microscopy, we found that the two essential subcomplexes of the proteasome, the regulatory (19S) and catalytic (20S) particles, are differentially distributed within individual rat cortical neurons. We discovered an unexpected abundance of free 19S particles near synapses. The free neuronal 19S particles bind and deubiquitylate lysine 63-ubiquitin (Lys63-ub), a non-proteasome-targeting ubiquitin linkage. Pull-down assays revealed a significant overrepresentation of synaptic molecules as Lys63-ub interactors. Inhibition of the 19S deubiquitylase activity significantly altered excitatory synaptic transmission and reduced the synaptic availability of AMPA receptors at multiple trafficking points in a proteasome-independent manner. Together, these results reveal a moonlighting function of the regulatory proteasomal subcomplex near synapses.
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