研究人员利用超分辨率显微镜发现，蛋白酶体的两个基本亚复合物，即调节性（19S）和催化性（20S）颗粒，在单个大鼠皮层神经元中的分布是不同的。研究人员在突触附近意外地发现了大量的游离19S颗粒。游离的神经元19S颗粒与赖氨酸63-泛素（Lys63-ub）结合并使其去泛素化，这是一种非细胞体靶向泛素连接。
Pull-down实验显示，突触分子作为Lys63-ub相互作用者的比例明显过高。抑制19S去泛素化酶的活性明显改变了兴奋性突触传递，并以独立于蛋白酶体的方式减少了AMPA受体在多个贩运点的突触可用性。这些结果共同揭示了调节蛋白酶体亚复合体在突触附近的兼职功能。
据介绍，蛋白酶体是细胞中主要的蛋白质降解机器，调节着神经元的突触和长期信息储存。
附：英文原文
Title: An abundance of free regulatory (19S) proteasome particles regulates neuronal synapses
Author: Chao Sun, Kristina Desch, Belquis Nassim-Assir, Stefano L. Giandomenico, Paulina Nemcova, Julian D. Langer, Erin M. Schuman
Issue&Volume: 2023-05-26
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.
DOI: adf2018
Source: https://www.science.org/doi/10.1126/science.adf2018