Vertebrate Cone Opsins Enable Sustained and Highly Sensitive Rapid Control of Gi/o Signaling in Anxiety Circuitry
Vertebrate Cone Opsins Enable Sustained and Highly Sensitive Rapid Control of Gi/o Signaling in Anxiety Circuitry
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DOI：
10.1016/j.neuron.2014.01.041
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发表时间：
2014-03-19
期刊：
影响因子：
16.2
通讯作者：
Herlitze, Stefan
中科院分区：
文献类型：
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作者：
Masseck, Olivia A.;Spoida, Katharina;Herlitze, Stefan
与G(I/O)信号通路偶联的G蛋白偶联受体(GPCRs)参与调控重要的生理功能，但由于工具的限制，难以精确地动力学和特异性地控制该信号通路。我们建立了两种脊椎动物视锥视蛋白，短波长视蛋白和长波长视蛋白，用于在体外和体内长时间重复激活G(I/O)信号通路。我们证明了这两种视蛋白在HEK细胞中对G(I/O)通路的重复快速、膜分隔、超光敏感和波长依赖的激活。我们还在脑片和体内显示了对中缝背核(DRN)5-HT1A受体区域G(I/O)通路激活的重复控制，这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G(I/O)偶联GPCRs在健康和疾病中的作用。
G protein-coupled receptors (GPCRs) coupling to G(i/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 G(i/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 G(i/o) pathway in HEK cells. We also show repetitive control of G(i/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 G(i/o)-coupled GPCRs in health and disease.