1 Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
2 School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
Neuroscientist. 2018 Dec;24(6):639-651. doi: 10.1177/1073858418762317. Epub 2018 Mar 12.
Cellular models of memory formation have focused on the need for protein synthesis. Recently, evidence has emerged that protein degradation mediated by the ubiquitin-proteasome system (UPS) is also important for this process. This has led to revised cellular models of memory formation that focus on a balance between protein degradation and synthesis. However, protein degradation is only one function of the UPS. Studies using single-celled organisms have shown that non-proteolytic ubiquitin-proteasome signaling is involved in histone modifications and DNA methylation, suggesting that ubiquitin and the proteasome can regulate chromatin remodeling independent of protein degradation. Despite this evidence, the idea that the UPS is more than a protein degradation pathway has not been examined in the context of memory formation. In this article, we summarize recent findings implicating protein degradation in memory formation and discuss various ways in which both ubiquitin signaling and the proteasome could act independently to regulate epigenetic-mediated transcriptional processes necessary for learning-dependent synaptic plasticity. We conclude by proposing comprehensive models of how non-proteolytic functions of the UPS could work in concert to control epigenetic regulation of the cellular memory consolidation process, which will serve as a framework for future studies examining the role of the UPS in memory formation.
记忆形成的细胞模型一直关注蛋白质合成的必要性。最近，有证据表明，泛素-蛋白酶体系统（UPS）介导的蛋白质降解对于这一过程也很重要。这导致了对记忆形成的细胞模型的修订，重点关注蛋白质降解和合成之间的平衡。然而，蛋白质降解只是 UPS 的一个功能。使用单细胞生物的研究表明，非蛋白水解泛素-蛋白酶体信号参与组蛋白修饰和 DNA 甲基化，这表明泛素和蛋白酶体可以独立于蛋白质降解来调节染色质重塑。尽管有这些证据，但 UPS 不仅仅是一种蛋白质降解途径的观点在记忆形成的背景下尚未得到检验。在本文中，我们总结了最近的发现，这些发现表明蛋白质降解在记忆形成中的作用，并讨论了泛素信号和蛋白酶体可以独立作用以调节学习依赖性突触可塑性所需的表观遗传介导的转录过程的各种方式。最后，我们提出了 UPS 的非蛋白水解功能如何协同作用以控制细胞记忆巩固过程的表观遗传调节的综合模型，这将作为未来研究 UPS 在记忆形成中的作用的框架。
