Activity-regulated growth of motoneurons at the neuromuscular junction is mediated by NADPH oxidases

Activity-regulated growth of motoneurons at the neuromuscular junction is mediated by NADPH oxidases
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神经肌肉接头处运动神经元的活动调节生长由 NADPH 氧化酶介导

DOI:
10.1101/2022.10.27.514147
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发表时间:
2022
期刊:
--
影响因子:
--
通讯作者:
Sobrido-Cameán D
Sobrido-Cameán D
中科院分区:
--
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作者:
Sobrido-Cameán D

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神经元以各种方式对它们所经历的活动水平的变化做出反应,包括突触前和突触后末端的结构变化。活性调节结构调整所需的基本可塑性信号是活性氧(ROS)。为了确定活性调节活性氧的来源所需的结构可塑性在vivowe使用果蝇幼虫神经肌肉接头作为一个高度听话的实验模型系统。对于突触前运动神经末梢的调整,我们发现需要NADPH氧化酶,Nox和双氧化酶(Duox),这是在果蝇基因组中编码的。这与Nox被排除在外的突触后树突形成对比。NADPH氧化酶产生ROS到细胞外空间。在这里,我们表明,两个水通道蛋白,Bib和滴水,是必要的活性氧导管在突触前运动神经元的活动调节,NADPH氧化酶依赖的变化,突触前运动神经元的终端增长。我们的数据进一步表明,不同方面的神经元活性调节的结构变化可能是由不同的活性氧来源调节:在bouton数的变化需要两个NADPH氧化酶,而活性调节的活性区的数量的变化可能是由其他来源的活性氧调制。总的来说,我们的研究结果表明,NADPH氧化酶作为重要的酶介导的活动调节神经元的可塑性调整。
Neurons respond to changes in the levels of activity they experience in a variety of ways, including structural changes at pre- and postsynaptic terminals. An essential plasticity signal required for such activity-regulated structural adjustments are reactive oxygen species (ROS). To identify sources of activity-regulated ROS required for structural plasticityin vivowe used the Drosophila larval neuromuscular junction as a highly tractable experimental model system. For adjustments of presynaptic motor terminals, we found a requirement for both NADPH oxidases, Nox and dual oxidase (Duox), that are encoded in the Drosophila genome. This contrasts with the postsynaptic dendrites from which Nox is excluded. NADPH oxidases generate ROS to the extracellular space. Here, we show that two aquaporins, Bib and Drip, are necessary ROS conduits in the presynaptic motoneuron for activity regulated, NADPH oxidase dependent changes in presynaptic motoneuron terminal growth. Our data further suggest that different aspects of neuronal activity-regulated structural changes might be regulated by different ROS sources: changes in bouton number require both NADPH oxidases, while activity-regulated changes in the number of active zones might be modulated by other sources of ROS. Overall, our results show NADPH oxidases as important enzymes for mediating activity-regulated plasticity adjustments in neurons.
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