FOXO Regulates Neuromuscular Junction Homeostasis During Drosophila Aging.
FOXO Regulates Neuromuscular Junction Homeostasis During Drosophila Aging.
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DOI：
10.3389/fnagi.2020.567861
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发表时间：
2020
影响因子：
4.8
通讯作者：
Bai H
中科院分区：
文献类型：
--
作者：
Birnbaum A;Sodders M;Bouska M;Chang K;Kang P;McNeill E;Bai H
转录因子foxo是已知的寿命延长和组织稳态的调节因子。它与许多物种的神经元过程的维持有关，并已被证明通过调节神经肌肉接头（NMJ）的细胞骨架灵活性和突触可塑性来促进年轻特征。然而，foxo在老化神经肌肉接头功能中的作用还有待确定。我们分析了成年果蝇foxo- null突变体腹侧纵肌，发现年轻的突变体表现出与老年野生型果蝇相似的形态学特征，如较大的bouton区域和较短的末端分支。我们还观察到的变化，轴突细胞骨架和积累的晚期内体在foxo无效突变体和运动神经元特异性foxo敲除苍蝇，类似于那些老年野生型。运动神经元特异性过表达foxo可以延迟NMJ形态的年龄依赖性变化，表明foxo负责在衰老过程中维持NMJ的完整性。通过遗传筛选，我们确定了几个下游因子介导的Foxo调节NMJ稳态，包括在MAPK通路中涉及的基因。有趣的是，p38的磷酸化在运动神经元特异性foxo敲除果蝇中增加，表明foxo作为p38/MAPK激活的抑制剂。我们的工作表明，foxo是NMJ稳态的关键调节因子，它可能通过抑制MAPK信号转导来维持NMJ的完整性。
The transcription factor foxo is a known regulator of lifespan extension and tissue homeostasis. It has been linked to the maintenance of neuronal processes across many species and has been shown to promote youthful characteristics by regulating cytoskeletal flexibility and synaptic plasticity at the neuromuscular junction (NMJ). However, the role of foxo in aging neuromuscular junction function has yet to be determined. We profiled adult Drosophila foxo- null mutant abdominal ventral longitudinal muscles and found that young mutants exhibited morphological profiles similar to those of aged wild-type flies, such as larger bouton areas and shorter terminal branches. We also observed changes to the axonal cytoskeleton and an accumulation of late endosomes in foxo null mutants and motor neuron-specific foxo knockdown flies, similar to those of aged wild-types. Motor neuron-specific overexpression of foxo can delay age-dependent changes to NMJ morphology, suggesting foxo is responsible for maintaining NMJ integrity during aging. Through genetic screening, we identify several downstream factors mediated through foxo-regulated NMJ homeostasis, including genes involved in the MAPK pathway. Interestingly, the phosphorylation of p38 was increased in the motor neuron-specific foxo knockdown flies, suggesting foxo acts as a suppressor of p38/MAPK activation. Our work reveals that foxo is a key regulator for NMJ homeostasis, and it may maintain NMJ integrity by repressing MAPK signaling.
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影响因子：
13.3
作者：
Chang K;Kang P;Liu Y;Huang K;Miao T;Sagona AP;Nezis IP;Bodmer R;Ocorr K;Bai H
通讯作者：
Bai H
影响因子：
3.1
作者：
Bergado, Jorge A.;Almaguer, William
通讯作者：
Almaguer, William
DOI：
10.1002/neu.20279
发表时间：
2006-09-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Hebbar, Sarita;Hall, Rachel E.;Fernandes, Joyce J.
通讯作者：
Fernandes, Joyce J.
影响因子：
2.5
作者：
Beramendi, Ana;Peron, Samantha;Cantera, Rafael
通讯作者：
Cantera, Rafael
影响因子：
9
作者：
Gibbs KL;Kalmar B;Rhymes ER;Fellows AD;Ahmed M;Whiting P;Davies CH;Greensmith L;Schiavo G
通讯作者：
Schiavo G