NADPH oxidase generated reactive oxygen species and aquaporin conduits mediate activity-regulated dendritic plasticity
NADPH oxidase generated reactive oxygen species and aquaporin conduits mediate activity-regulated dendritic plasticity
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DOI：
10.1101/2020.11.16.384487
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发表时间：
2020-11
期刊：
影响因子：
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通讯作者：
S. Dhawan;Philip Myers;M. Landgraf
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作者：
S. Dhawan;Philip Myers;M. Landgraf
神经元利用树突乔木的可塑性作为一个更大的适应性可塑性机制套件的一部分。这在果蝇胚胎和幼虫的运动神经元中得到了明确的体现，其中树突状乔木完全是突触后的，并被用作稳态装置，通过适应它们的生长和连接来补偿突触输入的变化。我们最近发现活性氧（ROS）作为新的可塑性信号，这种形式的树突状细胞的调整工具。ROS与神经元活性水平相关，并负调节树突乔木的大小。在这里，我们研究了NADPH氧化酶作为这种活性调节的ROS的潜在来源，并涉及双氧化酶（但不是Nox），它在细胞外产生过氧化氢。我们进一步表明，水通道蛋白比布和滴水，但不是普，所需的活性调节ROS介导的运动神经元树突乔木大小的调整。这些结果表明了一种模型，其中神经元活动导致NADPH氧化酶双氧化酶的激活，其在细胞外表面产生过氧化氢;水通道蛋白然后可能充当这些细胞外ROS被引导回到细胞中所必需的管道，在那里它们负调节树突状乔木的大小。
Neurons utilize plasticity of dendritic arbors as part of a larger suite of adaptive plasticity mechanisms. This explicitly manifests with motoneurons in the Drosophila embryo and larva, where dendritic arbors are exclusively postsynaptic and are used as homeostatic devices, compensating for changes in synaptic input through adapting their growth and connectivity. We recently identified reactive oxygen species (ROS) as novel plasticity signals instrumental in this form of dendritic adjustment. ROS correlate with levels of neuronal activity and negatively regulate dendritic arbor size. Here, we investigated NADPH oxidases as potential sources of such activity-regulated ROS and implicate Dual Oxidase (but not Nox), which generates hydrogen peroxide extracellularly. We further show that the aquaporins Bib and Drip, but not Prip, are required for activity-regulated ROS-mediated adjustments of dendritic arbor size in motoneurons. These results suggest a model whereby neuronal activity leads to activation of the NADPH oxidase Dual Oxidase, which generates hydrogen peroxide at the extracellular face; aquaporins might then act as conduits that are necessary for these extracellular ROS to be channeled back into the cell where they negatively regulate dendritic arbor size.