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单链光集成器用于映射G蛋白结合受体激动剂

Kayla Kroning^1,2, Noam Gannot^1,3, Xingyu Li^1,3,4

¹Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109.

Proceedings of the National Academy of Sciences of the United States of America

|April 22, 2024

概括

科学家们开发了新的蛋白质传感器,以追踪大脑中的G蛋白结合受体 (GPCR) 激动剂. 这项技术,SPOTall,能够精确地定位多巴胺和阿片类药物等神经调节剂,从而推进神经科学研究.

科学领域:

神经科学是一个神经科学.
分子生物学分子生物学
生物化学生物化学

背景情况:

G蛋白结合受体 (GPCRs) 对于调节多种神经调节者的作用至关重要,包括多巴胺,血清素,乙胆和阿片类药物.
了解GPCR激动剂的精确局部化对于解读它们对特定神经元通路的影响至关重要.
现有的方法可能缺乏特异性或模块化,无法全面地绘制大脑中的激动剂活性.

研究的目的:

设计一个多功能平台,用于创建能够检测GPCR激进分子局部化的单蛋白链集成器传感器.
为多重成像开发现有阿片类受体传感器 (SPOTIT) 的红色光变体.
将 SPOTIT 平台调整为一个更广泛的系统 (SPOTall),用于检测各种 GPCRs 的激动剂.

主要方法:

模块化,单蛋白链集成器传感器的工程.
开发红色光蛋白变体,以提高成像能力.
调整 SPOTIT 平台,以创建 SPOTall 设计,使其具有广泛的 GPCR 可用性.
在体内测试传感器功能,在小鼠模型中使用病毒传递.

主要成果:

成功设计用于多重成像的红色光SPOTIT传感器.
创建SPOTall平台,并开发用于β2-上腺素受体 (B2AR),多巴胺D1和肌肉2受体的传感器.
证明M-SPOTIT和B2AR-SPOTall在小鼠大脑中检测出源地注射的吗啡,异二醇和上腺素.
在体内检测特定激动剂的传感器有效性的验证.

结论:

该SPOTIT和SPOTall传感器设计平台提供了一个强大的工具,用于无偏见地检测合成和内源神经调节剂激活剂.
这项技术有助于研究GPCR信号传递和对抗剂在整个大脑中的定位.
该平台的模块化性质具有在神经科学研究中广泛应用的巨大潜力.

关键词:

G蛋白结合受体的受体是G蛋白结合受体的受体.光传感器是一个光传感器.集成器传感器传感器集成器神经调节器检测检测神经调节器检测

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G-protein Coupled Receptors

G-protein Coupled Receptors

G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.

G Protein-coupled Receptors

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...