Wang Lei, Yang Yini, Deng Fei, Yan Yuqi, Li Yulong
Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, Peking University, Beijing, China.
State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, China.
bioRxiv. 2025 Jun 3:2025.06.01.657218. doi: 10.1101/2025.06.01.657218.
Prostaglandin E2 (PGE2) is an important lipid signaling molecule that regulates a wide range of physiological and pathological processes. However, its dynamics during these processes are largely unknown due to the lack of tools to directly visualize PGE2 with high spatiotemporal resolution. Here, we developed and characterized a genetically encoded PGE2 sensor, which we call GRAB (PGE2-1.0), that has high specificity for PGE2, nanomolar affinity, rapid kinetics, and high spatial resolution when expressed both and . Using fiber-photometry recordings, we found that PGE2-1.0 can reliably monitor endogenous PGE2 dynamics in the preoptic area in the brain during acute inflammation. The wide-field imaging with PGE2-1.0 reveals spatial heterogeneity in cortex-wide PGE2 dynamics during acute inflammation and seizure. Thus, our PGE2-1.0 sensor can be used to detect endogenous PGE2 dynamics with high spatiotemporal resolution, providing a robust tool for studying PGE2 under specific physiological and pathological conditions.
前列腺素E2(PGE2)是一种重要的脂质信号分子,可调节多种生理和病理过程。然而,由于缺乏能够以高时空分辨率直接可视化PGE2的工具,其在这些过程中的动态变化在很大程度上尚不清楚。在此,我们开发并表征了一种基因编码的PGE2传感器,我们将其称为GRAB(PGE2-1.0),当在[具体位置1]和[具体位置2]表达时,它对PGE2具有高特异性、纳摩尔亲和力、快速动力学和高空间分辨率。通过纤维光度记录,我们发现PGE2-1.0能够可靠地监测急性炎症期间大脑视前区的内源性PGE2动态变化。使用PGE2-1.0进行的宽场成像揭示了急性炎症和癫痫发作期间全皮质PGE2动态变化的空间异质性。因此,我们的PGE2-1.0传感器可用于以高时空分辨率检测内源性PGE2动态变化,为在特定生理和病理条件下研究PGE2提供了一个强大的工具。