An abundance of free regulatory (19 S ) proteasome particles regulates neuronal synapses

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 (19 ) and catalytic (20 ) particles, are differential...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2023-05, Vol.380 (6647), p.eadf2018-eadf2018
Main Authors: Sun, Chao, Desch, Kristina, Nassim-Assir, Belquis, Giandomenico, Stefano L, Nemcova, Paulina, Langer, Julian D, Schuman, Erin M
Format: Article
Language:English
Subjects:
Animals
Assembly
Axons
Biodegradation
Brain slice preparation
Compartments
Confocal microscopy
Degradation
Dendrites
Homeostasis
Immunoprecipitation
Localization
Lysates
Lysine
Lysine - metabolism
Microscopy
Neurons
Neurons - metabolism
Plastic properties
Plasticity
Proteasome 20S
Proteasome 26S
Proteasome Endopeptidase Complex - metabolism
Proteasomes
Protein biosynthesis
Protein synthesis
Proteins
Proteolysis
Proteomes
Rats
Substrates
Synapses
Synapses - metabolism
Synaptic plasticity
Synaptic Transmission
Ubiquitin
Ubiquitin - metabolism
α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
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Summary: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 (19 ) and catalytic (20 ) particles, are differentially distributed within individual rat cortical neurons. We discovered an unexpected abundance of free 19 particles near synapses. The free neuronal 19 particles bind and deubiquitylate lysine 63-ubiquitin (Lys -ub), a non-proteasome-targeting ubiquitin linkage. Pull-down assays revealed a significant overrepresentation of synaptic molecules as Lys -ub interactors. Inhibition of the 19 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.
ISSN:0036-8075
1095-9203
DOI:10.1126/SCIENCE.ADF2018