FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption.
FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption.
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DOI：
10.1083/jcb.201105154
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发表时间：
2012-02-06
期刊：
影响因子：
--
通讯作者：
Broihier HT
中科院分区：
文献类型：
--
作者：
Nechipurenko IV;Broihier HT
FOXO抑制中枢神经系统中微管的稳定性，使其降解成为细胞对细胞骨架损伤保护性反应的重要组成部分。转录因子在发育过程中和轴突损伤后对神经元微管(MTS)的调节是必不可少的。在这篇文章中，我们发现了果蝇FoxO在神经肌肉接头(NMJ)限制MT稳定性的一种新的神经元功能。FOXO功能丧失的NMJ表现为MT稳定性增强。相反，野生型FoxO运动神经元的过度表达中度破坏了MTS的稳定，而结构性核FoxO的过度表达则严重破坏了MTS的稳定。因此，FoxO负性调节突触MT的稳定性。FOXO家族成员是压力激活反馈回路中公认的组成部分。我们推测，FoxO也可能受到细胞骨架应激的调节，因为它在细胞骨架损伤后处于形成神经元MT组织的良好位置。事实上，在急性药理性MT破坏以及神经元细胞骨架的持续遗传破坏后，神经元FoxO水平显著降低。这一下降不依赖于亮氨酸拉链激酶-瓦伦达双途径和Akt激酶所需的功能。我们提出了一个模型，在这个模型中，FoxO的降解是对细胞骨架侮辱的稳定、保护性反应的一个组成部分。
FoxO inhibits microtubule stability in the central nervous system, making its degradation an essential component of a cell’s protective response to cytoskeletal insult. Transcription factors are essential for regulating neuronal microtubules (MTs) during development and after axon damage. In this paper, we identify a novel neuronal function for Drosophila melanogaster FoxO in limiting MT stability at the neuromuscular junction (NMJ). foxO loss-of-function NMJs displayed augmented MT stability. In contrast, motor neuronal overexpression of wild-type FoxO moderately destabilized MTs, whereas overexpression of constitutively nuclear FoxO severely destabilized MTs. Thus, FoxO negatively regulates synaptic MT stability. FoxO family members are well-established components of stress-activated feedback loops. We hypothesized that FoxO might also be regulated by cytoskeletal stress because it was well situated to shape neuronal MT organization after cytoskeletal damage. Indeed, levels of neuronal FoxO were strongly reduced after acute pharmacological MT disruption as well as sustained genetic disruption of the neuronal cytoskeleton. This decrease was independent of the dual leucine zipper kinase–Wallenda pathway and required function of Akt kinase. We present a model wherein FoxO degradation is a component of a stabilizing, protective response to cytoskeletal insult.
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影响因子：
5.7
作者：
Dent EW;Merriam EB;Hu X
通讯作者：
Hu X
FOXO转录因子直接激活BIM基因表达并促进交感神经元中的凋亡。
影响因子：
7.8
作者：
Gilley, Jonathan;Coffer, Paul J;Ham, Jonathan
通讯作者：
Ham, Jonathan
影响因子：
16.2
作者：
Broihier, HT;Skeath, JB
通讯作者：
Skeath, JB
影响因子：
5.3
作者：
Franco, B;Bogdanik, L;Grau, Y
通讯作者：
Grau, Y
DOI：
10.1242/dev.069062
发表时间：
2011-12
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Christensen R;de la Torre-Ubieta L;Bonni A;Colón-Ramos DA
通讯作者：
Colón-Ramos DA