Regulation of synaptic nlg-1/neuroligin abundance by the skn-1/Nrf stress response pathway protects against oxidative stress.
Regulation of synaptic nlg-1/neuroligin abundance by the skn-1/Nrf stress response pathway protects against oxidative stress.
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DOI：
10.1371/journal.pgen.1004100
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发表时间：
2014-01
期刊：
影响因子：
4.5
通讯作者：
Sieburth D
中科院分区：
文献类型：
--
作者：
Staab TA;Evgrafov O;Knowles JA;Sieburth D
Nrf家族的转录因子介导的适应性反应的压力和寿命，但关键的Nrf目标的身份，以及组织中，他们在多细胞生物体中发挥作用，以促进生存，是未知的。在这里，我们使用全转录组RNA测序，以确定810个基因的表达控制的SKN-1/Nrf 2负调节WDR-23在秀丽隐杆线虫的神经系统。在这些基因中，有一个是突触细胞粘附分子nlg-1/neuroligin。我们发现NLG-1蛋白的突触丰度在产生氧化应激的药物治疗或skn-1的遗传激活后增加。增加nlg-1剂量与增加的生存率相关，而nlg-1的基因失活会降低生存率并损害skn-1介导的应激抗性。我们确定了一个典型的SKN-1结合位点的nlg-1的启动子，结合SKN-1在体外，是必要的SKN-1和毒素介导的增加nlg-1的表达在体内。总之，我们的研究结果表明，神经系统中的SKN-1激活可以通过直接调节nlg-1/neuroligin表达来保护生物体应对压力。生物体已经进化出在细胞水平上保护自己以应对各种环境压力的机制。氧化应激，由细胞产生的自由基和内源性抗氧化剂防御的不平衡引起，对神经系统特别有害。事实上，氧化应激水平的升高与几乎所有的神经退行性疾病有关。因此，了解生物如何从细胞到系统水平保护自己免受氧化应激是至关重要的。在这里，我们发现，增加的压力激活了一条途径，增加了神经元突触中某些蛋白质的数量。这提出了一个有趣的模型，在这个模型中，神经元对压力的反应可能是试图增强突触的强度以防止退化。
The Nrf family of transcription factors mediates adaptive responses to stress and longevity, but the identities of the crucial Nrf targets, and the tissues in which they function in multicellular organisms to promote survival, are not known. Here, we use whole transcriptome RNA sequencing to identify 810 genes whose expression is controlled by the SKN-1/Nrf2 negative regulator WDR-23 in the nervous system of Caenorhabditis elegans. Among the genes identified is the synaptic cell adhesion molecule nlg-1/neuroligin. We find that the synaptic abundance of NLG-1 protein increases following pharmacological treatments that generate oxidative stress or by the genetic activation of skn-1. Increasing nlg-1 dosage correlates with increased survival in response to oxidative stress, whereas genetic inactivation of nlg-1 reduces survival and impairs skn-1-mediated stress resistance. We identify a canonical SKN-1 binding site in the nlg-1 promoter that binds to SKN-1 in vitro and is necessary for SKN-1 and toxin-mediated increases in nlg-1 expression in vivo. Together, our results suggest that SKN-1 activation in the nervous system can confer protection to organisms in response to stress by directly regulating nlg-1/neuroligin expression. Organisms have evolved mechanisms to protect themselves at the cellular level in response to a variety of environmental stresses. Oxidative stress, caused by an imbalance in the cellular production of free radicals and endogenous antioxidant defenses, can be particularly detrimental to the nervous system. Indeed, elevated levels of oxidative stress have been linked to nearly all neurodegenerative diseases. Therefore, understanding how living creatures protect themselves against oxidative stress, from a cellular to a systemic level, is vital. Here, we have found that increased stress activates a pathway that increases the amount of certain proteins found at neuronal synapses. This presents an interesting model in which, in response to stress, neurons might attempt to enhance the strength of the synapse to prevent degeneration.
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影响因子：
3.7
作者：
Hasegawa K;Miwa J
通讯作者：
Miwa J
分析突触蛋白鉴定了胰岛素分泌和寿命的调节剂。
影响因子：
4.5
作者：
Ch'ng, QueeLim;Sieburth, Derek;Kaplan, Joshua M.
通讯作者：
Kaplan, Joshua M.
DOI：
10.1895/wormbook.1.5.2
发表时间：
2012-11-20
期刊：
WormBook : the online review of C. elegans biology
影响因子：
--
作者：
Blumenthal, Thomas
通讯作者：
Blumenthal, Thomas
影响因子：
5.3
作者：
Feng, ZW;Li, L;Porter, AG
通讯作者：
Porter, AG
影响因子：
4.3
作者：
Hunter, Jerrod W.;Mullen, Gregory P.;Rand, James B.
通讯作者：
Rand, James B.