Neuroscience Institute, Georgia State University, Atlanta, GA, USA; Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA, USA.
Neuropharmacology. 2021 Sep 15;196:108690. doi: 10.1016/j.neuropharm.2021.108690. Epub 2021 Jun 29.
Transcription-translation coupling leads to the production of proteins that are key for controlling essential neuronal processes that include neuronal development and changes in synaptic strength. Although these events have been a prevailing theme in neuroscience, the regulation of proteins via posttranslational signaling pathways are equally relevant for these neuronal processes. Ubiquitin is one type of posttranslational modification that covalently attaches to its targets/substrates. Ubiquitination of proteins play a key role in multiple signaling pathways, the predominant being removal of its substrates by a large molecular machine called the proteasome. Here, I review 40 years of progress on ubiquitination in the nervous system at glutamatergic synapses focusing on axon pathfinding, synapse formation, presynaptic release, dendritic spine formation, and regulation of postsynaptic glutamate receptors. Finally, I elucidate emerging themes in ubiquitin biology that may challenge our current understanding of ubiquitin signaling in the nervous system.
转录-翻译偶联导致产生蛋白质，这些蛋白质是控制关键神经元过程的关键，包括神经元发育和突触强度的变化。尽管这些事件一直是神经科学的一个主要主题，但通过翻译后信号通路对蛋白质的调节对于这些神经元过程同样重要。泛素是一种通过共价键连接到其靶标/底物的翻译后修饰物。蛋白质的泛素化在多种信号通路中起着关键作用，其中主要的是通过一种称为蛋白酶体的大型分子机器来去除其底物。在这里，我回顾了 40 年来在谷氨酸能突触中的神经系统中泛素化的进展，重点介绍了轴突寻路、突触形成、突触前释放、树突棘形成以及对突触后谷氨酸受体的调节。最后，我阐明了泛素生物学中的新主题，这些主题可能挑战我们目前对神经系统中泛素信号的理解。
