Genetically encoded tools for in vivo G-protein-coupled receptor agonist detection at cellular resolution.
Genetically encoded tools for in vivo G-protein-coupled receptor agonist detection at cellular resolution.
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DOI：
10.1002/ctm2.1124
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发表时间：
2022-12
影响因子：
10.6
通讯作者：
中科院分区：
文献类型：
--
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G蛋白偶联受体（GPCR）是人体中最丰富的受体类型，负责调节许多生理过程，如感觉，认知，肌肉收缩和代谢。此外，GPCR在脑中广泛表达，其中它们的激动剂构成大量神经递质和神经调质。由于GPCR在人类生理学中的重要性，基因编码的传感器已被工程化以在体内以细胞分辨率检测GPCR激动剂。这些传感器可以分为两大类：一类是提供GPCR激动剂信号动力学的真实的实时信息，另一类是将GPCR激动剂信号整合到永久的、可量化的标记中，可用于检测GPCR激动剂在大脑大区域中的定位。在这篇综述中，我们讨论了各种设计的真实的-时间和集成传感器，它们的优点和局限性，以及一些在体内的应用。我们还讨论了一起使用真实的时间和积分传感器来识别受内源性GPCR激动剂影响的神经元回路的潜力，并对这些回路中GPCR激动剂释放的时空动力学进行了详细的表征。通过一起使用这些传感器，可以扩展GPCR介导的信号传导的整体知识。G蛋白偶联受体（GPCR）激动剂传感器利用下游GPCR信号传导事件（例如GPCR构象变化和蛋白质结合）来给出可测量的传感器读数。
G‐protein‐coupled receptors (GPCRs) are the most abundant receptor type in the human body and are responsible for regulating many physiological processes, such as sensation, cognition, muscle contraction and metabolism. Further, GPCRs are widely expressed in the brain where their agonists make up a large number of neurotransmitters and neuromodulators. Due to the importance of GPCRs in human physiology, genetically encoded sensors have been engineered to detect GPCR agonists at cellular resolution in vivo. These sensors can be placed into two main categories: those that offer real‐time information on the signalling dynamics of GPCR agonists and those that integrate the GPCR agonist signal into a permanent, quantifiable mark that can be used to detect GPCR agonist localisation in a large brain area. In this review, we discuss the various designs of real‐time and integration sensors, their advantages and limitations, and some in vivo applications. We also discuss the potential of using real‐time and integrator sensors together to identify neuronal circuits affected by endogenous GPCR agonists and perform detailed characterisations of the spatiotemporal dynamics of GPCR agonist release in those circuits. By using these sensors together, the overall knowledge of GPCR‐mediated signalling can be expanded. G‐protein‐coupled receptor (GPCR) agonist sensors utilise downstream GPCR signalling events, such as GPCR conformational changes and protein binding, to give a measurable sensor readout.
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影响因子：
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