O-GlcNAc Signaling Orchestrates the Regenerative Response to Neuronal Injury in Caenorhabditis elegans.
O-GlcNAc Signaling Orchestrates the Regenerative Response to Neuronal Injury in Caenorhabditis elegans.
复制标题
O-GlcNAc 信号传导协调秀丽隐杆线虫神经元损伤的再生反应。
DOI：
10.1016/j.celrep.2018.07.078
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发表时间：
2018
期刊：
影响因子：
8.8
通讯作者：
Gabel,ChristopherV
中科院分区：
文献类型：
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作者：
Taub,DanielG;Awal,MehrajR;Gabel,ChristopherV
损伤后轴突的再生是一项固有的代谢任务。然而，影响损伤后修复的代谢调节机制还不清楚。O-连接的β-N-乙酰葡糖胺（O-GlcNAc）是丝氨酸和苏氨酸的翻译后修饰，其作为细胞营养素的传感器发挥作用。在秀丽隐杆线虫的vivolaser轴突切断术中，我们发现，O-GlcNAc转移酶或O-GlcNAc酶的破坏分别降低和增加O-GlcNAc水平，显著增加了神经元的再生。缺乏O-GlcNAc诱导胰岛素信号通路中的AKT-1分支使用糖酵解。相反，O-GlcNAc水平的增加激活胰岛素信号传导途径的相反分支，由此SGK-1调节FOXO转录因子β-16以影响线粒体功能。代谢途径之间这种切换样机制的存在表明O-GlcNAc信号传导传递细胞营养状态以协调受损神经元中的代谢并使再生反应最大化。
Regrowth of an axon after injury is an inherently metabolic undertaking. Yet the mechanisms of metabolic regulation that influence repair following injury are not well understood. O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients. Performingin vivolaser axotomies inCaenorhabditis elegans, we find that neuronal regeneration is substantially increased by disruptions of either the O-GlcNAc transferase or the O-GlcNAcase that decrease and increase O-GlcNAc levels, respectively. A lack of O-GlcNAc induces the AKT-1 branch in the insulin-signaling pathway to use glycolysis. In contrast, increased O-GlcNAc levels activate an opposing branch of the insulin-signaling pathway whereby SGK-1 modulates the FOXO transcription factor DAF-16 to influence mitochondrial function. The existence of this toggle-like mechanism between metabolic pathways suggests that O-GlcNAc signaling conveys cellular nutrient status to orchestrate metabolism in a damaged neuron and maximize the regenerative response.