A tool kit of highly selective and sensitive genetically encoded neuropeptide sensors

作者：Huan Wang, Tongrui Qian, Yulin Zhao, Yizhou Zhuo, Chunling Wu, Takuya Osakada, Peng Chen, Zijun Chen, Huixia Ren, Yuqi Yan, Lan Geng, Shengwei Fu, Long Mei, Guochuan Li, Ling Wu, Yiwen Jiang, Weiran Qian, Li Zhang, Wanling Peng, Min Xu, Ji Hu, Man Jiang, Liangyi Chen, Chao Tang, Yingjie Zhu, Dayu Lin, Jiang‐Ning Zhou, Yulong Li · 发表于：Science · 年份：2023 · DOI：10.1126/science.abq8173 · 被引用次数：138 · 研究领域：Receptor Mechanisms and Signaling、Neuropeptides and Animal Physiology、Lipid Membrane Structure and Behavior

Neuropeptides are key signaling molecules in the endocrine and nervous systems that regulate many critical physiological processes. Understanding the functions of neuropeptides in vivo requires the ability to monitor their dynamics with high specificity, sensitivity, and spatiotemporal resolution. However, this has been hindered by the lack of direct, sensitive, and noninvasive tools. We developed a series of GRAB (G protein-coupled receptor activation‒based) sensors for detecting somatostatin (SST), corticotropin-releasing factor (CRF), cholecystokinin (CCK), neuropeptide Y (NPY), neurotensin (NTS), and vasoactive intestinal peptide (VIP). These fluorescent sensors, which enable detection of specific neuropeptide binding at nanomolar concentrations, establish a robust tool kit for studying the release, function, and regulation of neuropeptides under both physiological and pathophysiological conditions.