Activity-dependent dynamics and sequestration of proteasomes in dendritic spines
Activity-dependent dynamics and sequestration of proteasomes in dendritic spines
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DOI：
10.1038/nature04769
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发表时间：
2006-06-28
期刊：
影响因子：
64.8
通讯作者：
Schuman, Erin M.
中科院分区：
文献类型：
--
作者：
Bingol, Baris;Schuman, Erin M.
通过泛素蛋白酶体途径调节的蛋白质降解正在成为突触功能和可塑性的重要调节剂（1-15）。蛋白酶体是一个大的，多亚基的细胞机器，识别，展开和降解目标多泛素化蛋白。在这里，我们报告NMDA（N-甲基-D-天冬氨酸）受体依赖的蛋白酶体从树突轴突触刺激后突触棘的重新分配，提供了一种机制，局部蛋白质降解。使用蛋白酶体活性报告和局部灌注，我们表明，突触刺激调节蛋白酶体活性局部树突。我们使用限制性光漂白的个人刺和树突状轴揭示的动力学基础蛋白酶体螯合，并表明活动适度提高蛋白酶体进入刺的速度，同时大大降低其退出率。蛋白酶体螯合是持久的，反映了与肌动蛋白为基础的细胞骨架。总之，我们的数据表明，突触活动可以促进蛋白酶体的募集和隔离，以局部重塑突触的蛋白质组成。
The regulated degradation of proteins by the ubiquitin proteasome pathway is emerging as an important modulator of synaptic function and plasticity(1-15). The proteasome is a large, multi-subunit cellular machine that recognizes, unfolds and degrades target polyubiquitinated proteins. Here we report NMDA (N-methyl-D-aspartate) receptor-dependent redistribution of proteasomes from dendritic shafts to synaptic spines upon synaptic stimulation, providing a mechanism for local protein degradation. Using a proteasome-activity reporter and local perfusion, we show that synaptic stimulation regulates proteasome activity locally in the dendrites. We used restricted photobleaching of individual spines and dendritic shafts to reveal the dynamics that underlie proteasome sequestration, and show that activity modestly enhances the entry rate of proteasomes into spines while dramatically reducing their exit rate. Proteasome sequestration is persistent, reflecting an association with the actin-based cytoskeleton. Together, our data indicate that synaptic activity can promote the recruitment and sequestration of proteasomes to locally remodel the protein composition of synapses.