Department of General Zoology and Neurobiology, ND7/31, Ruhr-University Bochum, Universitätsstrasse 150, 44780 Bochum, Germany.
INSERM, U968, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, CNRS, UMR_7210 Institut de la Vision, Paris, F-75012, France.
Neuron. 2014 Mar 19;81(6):1263-1273. doi: 10.1016/j.neuron.2014.01.041.
G protein-coupled receptors (GPCRs) coupling to Gi/o signaling pathways are involved in the control of important physiological functions, which are difficult to investigate because of the limitation of tools to control the signaling pathway with precise kinetics and specificity. We established two vertebrate cone opsins, short- and long-wavelength opsin, for long-lasting and repetitive activation of Gi/o signaling pathways in vitro and in vivo. We demonstrate for both opsins the repetitive fast, membrane-delimited, ultra light-sensitive, and wavelength-dependent activation of the Gi/o pathway in HEK cells. We also show repetitive control of Gi/o pathway activation in 5-HT1A receptor domains in the dorsal raphe nucleus (DRN) in brain slices and in vivo, which is sufficient to modulate anxiety behavior in mice. Thus, vertebrate cone opsins represent a class of tools for understanding the role of Gi/o-coupled GPCRs in health and disease.
G 蛋白偶联受体（GPCRs）与 Gi/o 信号通路偶联，参与重要生理功能的调控。由于缺乏精确控制信号通路的工具，因此难以对其进行研究。我们建立了两种脊椎动物视蛋白，即短波长视蛋白和长波长视蛋白，用于体外和体内 Gi/o 信号通路的持久和重复激活。我们证明了这两种视蛋白都可以在 HEK 细胞中快速、膜限定、超敏感且波长依赖地重复激活 Gi/o 通路。我们还表明，在脑切片和体内的背侧中缝核（DRN）中的 5-HT1A 受体结构域中，可以重复控制 Gi/o 通路的激活，这足以调节小鼠的焦虑行为。因此，脊椎动物视蛋白代表了一类工具，可用于了解 Gi/o 偶联 GPCR 在健康和疾病中的作用。
