Attenuation of insulin signalling contributes to FSN-1-mediated regulation of synapse development
Attenuation of insulin signalling contributes to FSN-1-mediated regulation of synapse development
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DOI：
10.1038/emboj.2013.91
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发表时间：
2013-06-12
期刊：
影响因子：
11.4
通讯作者：
Zhen, Mei
中科院分区：
文献类型：
--
作者：
Hung, Wesley L.;Hwang, Christine;Zhen, Mei
神经元F-box蛋白FSN-1通过负调节DLK介导的MAPK信号传导来调节秀丽隐杆线虫神经肌肉连接的发育。在本研究中，我们表明胰岛素/IGF信号的衰减也有助于FSN-1依赖性突触发育和功能。 FSN-1突变体中异常的突触形态和突触传播是通过减少突触后肌肉中的胰岛素/IGF-信号活性的部分和特异性挽救神经元中的配体INS-4和INS-6。 FSN-1与EGL-3体外的泛素化相互作用，并在体内降低EGL-3水平。我们建议FSN-1可以通过EGL-3依赖性胰岛素样配体加工来负调节胰岛素/IGF信号传导。
A neuronal F-box protein FSN-1 regulates Caenorhabditis elegans neuromuscular junction development by negatively regulating DLK-mediated MAPK signalling. In the present study, we show that attenuation of insulin/IGF signalling also contributes to FSN-1-dependent synaptic development and function. The aberrant synapse morphology and synaptic transmission in fsn-1 mutants are partially and specifically rescued by reducing insulin/IGF-signalling activity in postsynaptic muscles, as well as by reducing the activity of EGL-3, a prohormone convertase that processes agonistic insulin/IGF ligands INS-4 and INS-6, in neurons. FSN-1 interacts with, and potentiates the ubiquitination of EGL-3 in vitro, and reduces the EGL-3 level in vivo. We propose that FSN-1 may negatively regulate insulin/IGF signalling, in part, through EGL-3-dependent insulin-like ligand processing.