Bao Hong, Reist Noreen E, Zhang Bing
Department of Zoology, University of Oklahoma, Norman, OK 73019, USA.
Traffic. 2008 Dec;9(12):2190-205. doi: 10.1111/j.1600-0854.2008.00832.x. Epub 2008 Sep 15.
The ubiquitin-proteasome system plays an important role in synaptic development and function. However, many components of this system, and how they act to affect synapses, are still not well understood. In this study, we use the Drosophila neuromuscular junction to study the in vivo function of Liquid facets (Lqf), a homolog of mammalian epsin 1. Our data show that Lqf plays a novel role in synapse development and function. Contrary to prior models, Lqf is not required for clathrin-mediated endocytosis of synaptic vesicles. Lqf is required to maintain bouton size and shape and to sustain synapse growth by acting as a specific substrate of the deubiquitinating enzyme Fat facets. However, Lqf is not a substrate of the Highwire (Hiw) E3 ubiquitin ligase; neither is it required for synapse overgrowth in hiw mutants. Interestingly, Lqf converges on the Hiw pathway by negatively regulating transmitter release in the hiw mutant. These observations demonstrate that Lqf plays distinct roles in two ubiquitin pathways to regulate structural and functional plasticity of the synapse.
泛素 - 蛋白酶体系统在突触发育和功能中发挥着重要作用。然而，该系统的许多组成部分以及它们如何影响突触的作用，仍未得到充分理解。在本研究中，我们利用果蝇神经肌肉接头来研究哺乳动物 epsin 1 的同源物 Liquid facets（Lqf）在体内的功能。我们的数据表明，Lqf 在突触发育和功能中发挥着新的作用。与先前的模型相反，Lqf 对于网格蛋白介导的突触小泡内吞作用并非必需。Lqf 通过作为去泛素化酶 Fat facets 的特定底物来维持突触小体的大小和形状，并维持突触生长。然而，Lqf 不是 Highwire（Hiw）E3 泛素连接酶的底物；在 hiw 突变体中，突触过度生长也不需要 Lqf。有趣的是，Lqf 通过负向调节 hiw 突变体中的递质释放而汇聚到 Hiw 途径上。这些观察结果表明，Lqf 在两条泛素途径中发挥着不同的作用，以调节突触的结构和功能可塑性。
