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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.

bioRxiv : the preprint server for biology

|July 3, 2023

概括

新的SPOTall传感器可以检测整个大脑中的G蛋白结合受体 (GPCR) 激动剂局部. 这一平台能够无偏见地检测神经调节剂,进步神经科学研究.

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
药理学药理学是指药理学的学科.

背景情况:

G蛋白结合受体 (GPCRs) 调节关键神经调节者的作用,如多巴胺,血清素和阿片类药物.
了解GPCR激动剂的精确局部化对于破译它们对神经元通路的影响至关重要.

研究的目的:

推出一个新的平台,SPOTall,用于工程单蛋白链集成器传感器.
为了确定整个大脑的GPCR激进分子局部.
扩大用于检测更广泛的合成和内源神经调节器的工具包.

主要方法:

开发SPOTall传感器设计平台的开发.
对于β-2-上腺素受体 (B2AR),多巴胺受体D1和肌肉激素2激动剂的传感器的工程.
用于多重成像的SPOTIT传感器的红色光变体的工程.
使用M-SPOTIT和B2AR-SPOTall传感器在小鼠大脑中体内检测吗啡,异二醇和上腺素.

主要成果:

成功设计了针对B2AR,多巴胺D1和肌肉2受体的SPOTall传感器.
用红色光SPOTIT传感器展示多重成像能力.
验证M-SPOTIT和B2AR-SPOTall用于检测小鼠大脑中的特定激动剂.
建立一个多功能平台,用于检测GPCR激进分子.

结论:

SPOTall平台提供了一个多功能工具,用于创建GPCR集成器传感器.
这项技术使各种合成和内源神经调节剂的无偏见,全脑检测成为可能.
推动了对神经调节和药物作用在大脑中的研究.

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相关概念视频

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...