Ubiquitination-dependent mechanisms regulate synaptic growth and function
Ubiquitination-dependent mechanisms regulate synaptic growth and function
复制标题
DOI：
10.1038/35086595
复制
发表时间：
2001-07-26
期刊：
影响因子：
64.8
通讯作者：
Goodman, CS
中科院分区：
文献类型：
--
作者：
DiAntonio, A;Haghighi, AP;Goodman, CS
泛素与细胞蛋白质的共价连接是控制蛋白质活性和定位的有力机制（1）。泛素化是由泛素连接酶促进并由去泛素化蛋白酶拮抗的可逆修饰（2）。泛素依赖性机制调节许多重要过程，包括细胞周期进程、凋亡和转录调节（3）。在这里，我们表明，泛素依赖性机制调节果蝇神经肌肉接头（NMJ）的突触发育。去泛素化蛋白酶脂肪小面的神经元过表达（4）导致突触生长控制的严重破坏;突触终扣数量大量增加，突触分支模式精细化，以及突触功能的破坏。通过表达酵母去泛素化蛋白酶UBP 2（参考文献5）来拮抗神经元中的泛素化途径也会产生突触过度生长和功能障碍。脂肪小面和highwire（一种与泛素连接酶家族具有结构同源性的突触生长负调控因子）之间的遗传相互作用表明，突触发育可能受泛素化正调控因子和负调控因子之间的平衡控制。
The covalent attachment of ubiquitin to cellular proteins is a powerful mechanism for controlling protein activity and localization(1). Ubiquitination is a reversible modification promoted by ubiquitin ligases and antagonized by deubiquitinating proteases(2). Ubiquitin-dependent mechanisms regulate many important processes including cell-cycle progression, apoptosis and transcriptional regulation(3). Here we show that ubiquitin-dependent mechanisms regulate synaptic development at the Drosophila neuromuscular junction (NMJ). Neuronal overexpression of the deubiquitinating protease fat facets(4) leads to a profound disruption of synaptic growth control; there is a large increase in the number of synaptic boutons, an elaboration of the synaptic branching pattern, and a disruption of synaptic function. Antagonizing the ubiquitination pathway in neurons by expression of the yeast deubiquitinating protease UBP2 (ref. 5) also produces synaptic overgrowth and dysfunction. Genetic interactions between fat facets and highwire(6), a negative regulator of synaptic growth that has structural homology to a family of ubiquitin ligases, suggest that synaptic development may be controlled by the balance between positive and negative regulators of ubiquitination.