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

Author:

Sun Chao1ORCID,Desch Kristina1,Nassim-Assir Belquis1,Giandomenico Stefano L.1ORCID,Nemcova Paulina1ORCID,Langer Julian D.12ORCID,Schuman Erin M.1ORCID

Affiliation:

1. Max Planck Institute for Brain Research, 60438 Frankfurt am Main, Germany.

2. Max Planck Institute for Biophysics, 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 (19 S ) and catalytic (20 S ) particles, are differentially distributed within individual rat cortical neurons. We discovered an unexpected abundance of free 19 S particles near synapses. The free neuronal 19 S particles bind and deubiquitylate lysine 63–ubiquitin (Lys 63 -ub), a non–proteasome-targeting ubiquitin linkage. Pull-down assays revealed a significant overrepresentation of synaptic molecules as Lys 63 -ub interactors. Inhibition of the 19 S 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3