Aquaporin-4 (AQP4) facilitates water transport across astrocytic membranes in the brain, forming highly structured nanometric arrays. AQP4 has a central role in regulating cerebrospinal fluid (CSF) circulation and facilitating the clearance of solutes from the extracellular space of the brain. Adrenergic signaling has been shown to modulate the volume of the extracellular space of the brain via AQP4 localized at the end-feet of astrocytes, but the mechanisms by which AQP4 regulates CSF inflow and outflow in the brain remain elusive. Using advanced imaging techniques, including super-resolution microscopy and single-molecule tracking, we investigated the hypothesis that β-adrenergic receptor activation induces cellular changes that regulate AQP4 array size and mobility, thus influencing water transport in the brain. We report that the β-adrenergic agonist, isoproterenol hydrochloride, decreases AQP4 array size and enhances its membrane mobility, while hyperosmotic conditions induce the formation of larger, less mobile arrays. These findings reveal that AQP4 arrays are dynamic structures, responsive to adrenergic signals and osmotic changes, highlighting a novel regulatory mechanism of water transport in the brain. Our results provide insights into the molecular control of CSF circulation and extracellular brain space volume, laying the groundwork for understanding the relationship between astrocyte water transport, sleep physiology, and neurodegeneration.

中文翻译：

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星形胶质细胞中水通道蛋白 4 阵列动力学的单分子成像

Aquaporin-4 (AQP4) 促进水穿过大脑星形胶质细胞膜的运输，形成高度结构化的纳米阵列。 AQP4 在调节脑脊液 (CSF) 循环和促进大脑细胞外间隙溶质清除方面发挥着核心作用。肾上腺素信号传导已被证明可以通过位于星形胶质细胞末端的 AQP4调节大脑细胞外空间的体积，但 AQP4 调节大脑中 CSF 流入和流出的机制仍然难以捉摸。使用先进的成像技术，包括超分辨率显微镜和单分子追踪，我们研究了这样的假设：β-肾上腺素受体激活会诱导细胞变化，从而调节 AQP4 阵列的大小和流动性，从而影响大脑中的水运输。我们报告称，β-肾上腺素能激动剂盐酸异丙肾上腺素可减小 AQP4 阵列的尺寸并增强其膜的迁移性，而高渗条件会诱导形成更大、移动性更差的阵列。这些发现表明，AQP4 阵列是动态结构，对肾上腺素信号和渗透压变化做出反应，突出了大脑中水运输的一种新的调节机制。我们的结果提供了对脑脊液循环和细胞外脑空间体积的分子控制的见解，为理解星形胶质细胞水运输、睡眠生理学和神经退行性变之间的关系奠定了基础。