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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DOI：
10.3389/fncel.2022.1106593
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发表时间：
2022
影响因子：
5.3
通讯作者：
Landgraf, Matthias
中科院分区：
文献类型：
--
作者：
Sobrido-Camean, Daniel;Oswald, Matthew C. W.;Bailey, David M. D.;Mukherjee, Amrita;Landgraf, Matthias
关键词：
神经元以各种方式对它们所经历的活动水平的变化作出反应，包括突触前和突触后末端的结构变化。这种活性调节的结构调整所需的基本可塑性信号是活性氧（ROS）。为了确定体内结构可塑性所需的活性调节活性氧的来源，我们使用果蝇幼虫神经肌肉连接处作为高度可处理的实验模型系统。对于突触前运动末端的调节，我们发现NADPH氧化酶Nox和双氧化酶（Duox）都需要在果蝇基因组中编码。这与诺克斯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，我们发现两个水通道蛋白，Bib和Drip，是突触前运动神经元中必需的ROS通道，用于活性调节，NADPH氧化酶依赖性突触前运动神经元末端生长的变化。我们的数据进一步表明，神经元活动调节的结构变化的不同方面可能受到不同ROS来源的调节：钮扣数量的变化需要NADPH氧化酶，而活动调节的活性区数量的变化可能受到其他ROS来源的调节。总的来说，我们的结果表明NADPH氧化酶是介导神经元活动调节可塑性调节的重要酶。
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 plasticity in vivo we 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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