Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH 1015 Lausanne, Switzerland.
Int J Biochem Cell Biol. 2013 Mar;45(3):706-10. doi: 10.1016/j.biocel.2012.12.006. Epub 2012 Dec 20.
Ubiquitination of proteins by the Nedd4 family of ubiquitin ligases is a significant mechanism in protein trafficking and degradation and provides for tight spatiotemporal regulation. Ubiquitination is gaining increasing recognition as a central mechanism underpinning the regulation of neuronal development and homeostasis in the brain. This review will focus on the Nedd4 and Nedd4-2 E3 ubiquitin ligases that are implicated in an increasing number of neuronal protein-protein interactions. Understanding of the contribution of Nedd4 and Nedd4-2 in regulating key functions in the brain is shedding new light on the ubiquitination signal not only in orchestrating degradation events but also in protein trafficking. Furthermore, the description of several novel Nedd4/4-2 targets in neurons is changing the way we conceptualize how neurons maintain normal function and how this is altered in disease.
蛋白质的泛素化由 Nedd4 家族的泛素连接酶完成，这是蛋白质运输和降解的重要机制，并提供了严格的时空调节。泛素化作为调节大脑中神经元发育和稳态的核心机制，正受到越来越多的关注。本篇综述将聚焦于 Nedd4 和 Nedd4-2 E3 泛素连接酶，它们与越来越多的神经元蛋白-蛋白相互作用有关。对 Nedd4 和 Nedd4-2 在调节大脑关键功能中的作用的理解，不仅揭示了泛素化信号在协调降解事件中的作用，也揭示了其在蛋白质运输中的作用。此外，对神经元中几个新的 Nedd4/4-2 靶标的描述正在改变我们对神经元维持正常功能的方式的认识，以及这种方式在疾病中是如何改变的。
