Optical Approaches for Investigating Neuromodulation and G Protein-Coupled Receptor Signaling.
Optical Approaches for Investigating Neuromodulation and G Protein-Coupled Receptor Signaling.
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DOI：
10.1124/pharmrev.122.000584
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发表时间：
2023-11
影响因子：
21.1
通讯作者：
中科院分区：
文献类型：
--
作者：
尽管美国食品和药物管理局（FDA）批准的所有药物治疗中约有40%靶向G蛋白偶联受体（GPCR），但我们对这些受体在系统水平上的生理和功能作用的理解仍然存在差距。尽管异源表达系统和体外试验已经揭示了大量关于GPCR信号级联的信息，但这些级联如何在细胞类型、组织和器官系统之间相互作用仍然不清楚。经典的行为药理学实验缺乏时间和空间分辨率来解决这些长期存在的问题。在过去的半个世纪中，人们一直在努力开发用于理解GPCR信号传导的光学工具。从最初的配体释放方法到光遗传学技术的最新发展，这些策略使研究人员能够在体内和体外探索GPCR药理学中长期存在的问题。这些工具已被用于整个生物系统，并允许从特定的分子内事件到药理学在系统水平上以时空特定的方式进行询问。在这篇综述中，我们提出了一个历史的观点，背后的动机和发展的各种光学工具包，已产生的探测GPCR信号。在这里，我们强调了这些工具如何在体内用于揭示不同群体的GPCR及其信号级联在系统水平上的功能作用。G蛋白偶联受体（GPCR）仍然是药物干预的最有针对性的蛋白质类别之一，但我们对其独特的信号级联如何在系统水平上影响生理和行为的理解仍然有限。在这篇综述中，我们讨论了大量的光学技术，已被设计成探测GPCR信号在体外和体内。
Despite the fact that roughly 40% of all US Food and Drug Administration (FDA)-approved pharmacological therapeutics target G protein–coupled receptors (GPCRs), there remains a gap in our understanding of the physiologic and functional role of these receptors at the systems level. Although heterologous expression systems and in vitro assays have revealed a tremendous amount about GPCR signaling cascades, how these cascades interact across cell types, tissues, and organ systems remains obscure. Classic behavioral pharmacology experiments lack both the temporal and spatial resolution to resolve these long-standing issues. Over the past half century, there has been a concerted effort toward the development of optical tools for understanding GPCR signaling. From initial ligand uncaging approaches to more recent development of optogenetic techniques, these strategies have allowed researchers to probe longstanding questions in GPCR pharmacology both in vivo and in vitro. These tools have been employed across biologic systems and have allowed for interrogation of everything from specific intramolecular events to pharmacology at the systems level in a spatiotemporally specific manner. In this review, we present a historical perspective on the motivation behind and development of a variety of optical toolkits that have been generated to probe GPCR signaling. Here we highlight how these tools have been used in vivo to uncover the functional role of distinct populations of GPCRs and their signaling cascades at a systems level. G protein–coupled receptors (GPCRs) remain one of the most targeted classes of proteins for pharmaceutical intervention, yet we still have a limited understanding of how their unique signaling cascades effect physiology and behavior at the systems level. In this review, we discuss a vast array of optical techniques that have been devised to probe GPCR signaling both in vitro and in vivo.
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影响因子：
4.6
作者：
Yu G;Onodera H;Aono Y;Kawano F;Ueda Y;Furuya A;Suzuki H;Sato M
通讯作者：
Sato M
影响因子：
16.6
作者：
Broichhagen, Johannes;Johnston, Natalie R.;von Ohlen, Yorrick;Meyer-Berg, Helena;Jones, Ben J.;Bloom, Stephen R.;Rutter, Guy A.;Trauner, Dirk;Hodson, David J.
通讯作者：
Hodson, David J.
影响因子：
64.8
作者：
BOWNDS, D
通讯作者：
BOWNDS, D
DOI：
10.1073/pnas.68.8.1820
发表时间：
1971-01-01
影响因子：
11.1
作者：
BARTELS, E;WASSERMANN, NH;ERLANGER, BF
通讯作者：
ERLANGER, BF
影响因子：
25
作者：
Boyden, ES;Zhang, F;Deisseroth, K
通讯作者：
Deisseroth, K