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Vertebrate cone opsins enable sustained and highly sensitive rapid control of gi/o signaling in anxiety circuitry

机译:椎骨视锥蛋白能够持续,高度灵敏地快速控制焦虑电路中的gi / o信号

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摘要

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 invitro and invivo. 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 invivo, 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.
机译:与Gi / o信号通路偶联的G蛋白偶联受体(GPCR)参与重要的生理功能控制,由于用于精确控制动力学和特异性的信号通路控制工具的局限性,很难进行研究。我们建立了两个脊椎动物锥视蛋白,短和长波长视蛋白,用于体外和体内Gi / o信号通路的持久和重复激活。我们展示了两种视蛋白在HEK细胞中Gi / o途径的重复快速,膜定界,超光敏感和波长依赖的激活。我们还显示了脑切片和体内的背缝核(DRN)的5-HT1A受体域中的Gi / o途径激活的重复控制,足以调节小鼠的焦虑行为。因此,脊椎动物视锥蛋白代表了一类工具,用于理解Gi / o偶联GPCR在健康和疾病中的作用。

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