An Abundance of Free Proteasomal Regulatory (19S) Particles Regulate Neuronal Synapses Independent of the Proteasome
An Abundance of Free Proteasomal Regulatory (19S) Particles Regulate Neuronal Synapses Independent of the Proteasome
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 super-resolution 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.
Sun Chao、Giandomenico Stefano L.、Langer Julian D.、Desch Kristina、Nassim-Assir Belquis、Schuman Erin M.、Nemcova Paulina
基础医学神经病学、精神病学分子生物学
Sun Chao,Giandomenico Stefano L.,Langer Julian D.,Desch Kristina,Nassim-Assir Belquis,Schuman Erin M.,Nemcova Paulina.An Abundance of Free Proteasomal Regulatory (19S) Particles Regulate Neuronal Synapses Independent of the Proteasome[EB/OL].(2025-03-28)[2025-05-18].https://www.biorxiv.org/content/10.1101/2022.10.17.512557.点此复制
评论