A self-inactivating invertebrate opsin with resistance to retinal depletion optically drives biased signaling toward Gβγ-dependent ion channel modulation
A self-inactivating invertebrate opsin with resistance to retinal depletion optically drives biased signaling toward Gβγ-dependent ion channel modulation
复制标题
具有抗视网膜损耗的自失活无脊椎动物视蛋白以光学方式驱动偏向信号传导至 Gβγ 依赖性离子通道调制
DOI：
10.1101/2023.01.05.522954
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Kubo Yoshihiro
中科院分区：
文献类型：
--
作者：
Tsukamoto Hisao;Kubo Yoshihiro
动物视蛋白是一种光敏的G蛋白偶联受体(GPCRs)，已被用作光遗传学工具来控制G蛋白依赖的信号通路。在G蛋白激活后，GA和Gβγ亚基驱动不同的细胞内信号通路，导致复杂的细胞反应。为了某些目的，依赖于Ga和Gβγ的信号需要单独调制，但由于GA和Gβγ的化学计量比为1：1，这些反应是同时激发的。然而，我们发现G蛋白的时间激活使用自失活的无脊椎动物视蛋白Platynereisc-opsin1，通过利用Gβγ依赖和GA依赖的反应之间的动力学差异，以光依赖的方式驱动Gβγ依赖的GIRK通道激活的偏向信号。视蛋白诱导的瞬时Gi/o激活较好地导致动力学上快速的Gβγ依赖的Girk通道的激活，而不是较慢的Gi/oα依赖的腺苷环化酶抑制。尽管在自激活的脊椎动物视色素中也观察到了类似的Gβγ偏向信号特性，但Platynereisc-opsin1需要更少的视网膜分子来激发细胞反应。此外，Platynereisc-opsinl偏向于Gβγ的信号特性通过与加速G蛋白失活的RGS8蛋白的基因融合而得到增强。自失活的无脊椎动物视蛋白及其融合蛋白RGS8可以作为偏向于G-βγ依赖的离子通道调节的光学控制工具。
Animal opsins, light-sensitive G protein-coupled receptors (GPCRs), have been utilized for optogenetic tools to control G protein-dependent signaling pathways. Upon G protein activation, the Ga and Gβγ subunits drive different intracellular signaling pathways, leading to complex cellular responses. For some purposes, Ga-, Gβγ-dependent signaling needs to be separately modulated, but these responses are simultaneously evoked due to the 1:1 stoichiometry of Ga and Gβγ. Nevertheless, we show temporal activation of G protein using a self-inactivating invertebrate opsin,Platynereisc-opsin1, drives biased signaling for Gβγ-dependent GIRK channel activation in a light-dependent manner by utilizing the kinetic difference between Gβγ-dependent and Ga-dependent responses. The opsin-induced transient Gi/o activation preferably causes activation of the kinetically-fast Gβγ-dependent GIRK channels rather than slower Gi/oα-dependent adenylyl cyclase inhibition. Although similar Gβγ-biased signaling properties were observed in a selfinactivating vertebrate visual pigment,Platynereisc-opsin1 needs fewer retinal molecules to evoke cellular responses. Furthermore, the Gβγ-biased signaling properties ofPlatynereisc-opsinl are enhanced by genetically fused with RGS8 protein which accelerates G protein inactivation. The self-inactivating invertebrate opsin and its RGS8-fusion protein can function as optical control tools biased for Gβγ-dependent ion channel modulation.
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影响因子：
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作者：
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影响因子：
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影响因子：
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影响因子：
7.7
作者：
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