RT Journal Article
SR Electronic
T1 An Abundance of Free Proteasomal Regulatory (19S) Particles Regulate Neuronal Synapses Independent of the Proteasome
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.10.17.512557
DO 10.1101/2022.10.17.512557
A1 Chao Sun
A1 Kristina Desch
A1 Belquis Nassim-Assir
A1 Stefano L. Giandomenico
A1 Paulina Nemcova
A1 Julian D. Langer
A1 Erin M. Schuman
YR 2022
UL http://biorxiv.org/content/early/2022/10/17/2022.10.17.512557.abstract
AB The major protein-degradation machine, the proteasome, functions at brain synapses and regulates long-term information storage. Here we found that the two essential subcomplexes of the proteasome, the regulatory (19S) and catalytic (20S) particles that recognize and degrade substrates, are differentially distributed within individual rat cortical neurons. Using superresolution microscopy, we discovered a surprising abundance of free particles (19S) near synapses. The free neuronal 19S particles bind and deubiquitylate Lys63-ubiquitin, a non-proteasome targeting ub-linkage. Pull-down assays revealed a significant over-representation of synaptic molecules as Lys63 interactors. Inhibition of 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.One-Sentence Summary The 19S subcomplex of the major protein-degradation machine, the proteasome, functions without its 20S partner to populate and regulate synapses.Competing Interest StatementThe authors have declared no competing interest.