Ambrozkiewicz Mateusz Cyryl, Kawabe Hiroshi
Max Planck Institute of Experimental Medicine, Department of Molecular Neurobiology, Hermann-Rein-Straße 3, D-37075 Göttingen, Germany.
FEBS Lett. 2015 Jun 22;589(14):1635-43. doi: 10.1016/j.febslet.2015.05.009. Epub 2015 May 13.
The development of neurons is precisely controlled. Nerve cells are born from progenitor cells, migrate to their future target sites, extend dendrites and an axon to form synapses, and thus establish neural networks. All these processes are governed by multiple intracellular signaling cascades, among which ubiquitylation has emerged as a potent regulatory principle that determines protein function and turnover. Dysfunctions of E3 ubiquitin ligases or aberrant ubiquitin signaling contribute to a variety of brain disorders like X-linked mental retardation, schizophrenia, autism or Parkinson's disease. In this review, we summarize recent findings about molecular pathways that involve E3 ligases of the Homologous to E6-AP C-terminus (HECT) family and that control neuritogenesis, neuronal polarity formation, and synaptic transmission.
神经元的发育受到精确控制。神经细胞由祖细胞产生，迁移到其未来的靶位点，延伸树突和轴突以形成突触，从而建立神经网络。所有这些过程都由多个细胞内信号级联反应控制，其中泛素化已成为一种强大的调节机制，可决定蛋白质的功能和周转。E3泛素连接酶功能失调或异常的泛素信号传导会导致多种脑部疾病，如X连锁智力迟钝、精神分裂症、自闭症或帕金森病。在本综述中，我们总结了有关涉及E6相关蛋白C末端同源物（HECT）家族E3连接酶并控制神经突发生、神经元极性形成和突触传递的分子途径的最新发现。
