A Neuropsin-based Optogenetic Tool for Precise Control of G q signaling
A Neuropsin-based Optogenetic Tool for Precise Control of G q signaling
Abstract Gq-coupled receptors regulate numerous physiological processes by activating enzymes and inducing intracellular Ca2+ signals. There is a strong need for an optogenetic tool that enables powerful experimental control over Gq signaling. Here, we present chicken opsin 5 (cOpn5) as the long sought-after, single-component optogenetic tool that mediates ultra-sensitive optical control of intracellular Gq signaling with high temporal and spatial resolution. Expressing cOpn5 in mammalian cells enables blue light-triggered, Gq-dependent Ca2+ release from intracellular stores and protein kinase C activation. Strong Ca2+ transients were evoked by brief light pulses of merely 10 ms duration and at 3 orders lower light intensity of that for common optogenetic tools. Photostimulation of cOpn5-expressing cells at the subcellular and single-cell levels generated intracellular and intercellular Ca2+ wave propagation, respectively, thus demonstrating the high spatial precision of cOpn5 optogenetics. The cOpn5-mediated optogenetics could also be applied to activate neurons and control animal behavior in a circuit-dependent manner. We further revealed that optogenetic activation of cOpn5-expressing astrocytes induced massive ATP release and modulation neuronal activation in the brain of awake, behaving mice. cOpn5 optogenetics may find broad applications in studying the mechanisms and functional relevance of Gq signaling in both non-excitable cells and excitable cells in all major organ systems.
Wu Zhaofa、Zou Haiyue、Wu Wenting、Gao Xinwei、Wang Shu、Ren Yuqi、Weng Danwei、Guo Qingchun、Dai Ruicheng、Li Heng、Li Yulong、Qi Zhongyang、Yu Tao、Cui Yuting、Luo Minmin
State Key Laboratory of Membrane Biology, Peking University School of Life Sciences||PKU-McGovern Institute for Brain ResearchAcademy for Advanced Interdisciplinary Studies, Peking University||Chinese Institute for Brain ResearchSchool of Life Sciences, Tsinghua University||National Institute of Biological Sciences (NIBS)||Peking University-Tsinghua University-NIBS Joint Graduate ProgramChinese Institute for Brain ResearchChinese Institute for Brain ResearchNational Institute of Biological Sciences (NIBS)Graduate School of Peking Union Medical College||National Institute of Biological Sciences (NIBS)Capital Medical University||Chinese Institute for Brain ResearchSchool of Life Sciences, Peking University||National Institute of Biological Sciences (NIBS)||Peking University-Tsinghua University-NIBS Joint Graduate ProgramSchool of Life Sciences, Tsinghua University||National Institute of Biological Sciences (NIBS)||Tsinghua Institute of Multidisciplinary Biomedical Research (TIMBR)State Key Laboratory of Membrane Biology, Peking University School of Life Sciences||PKU-McGovern Institute for Brain ResearchNational Institute of Biological Sciences (NIBS)School of Life Sciences, Tsinghua University||National Institute of Biological Sciences (NIBS)||Peking University-Tsinghua University-NIBS Joint Graduate ProgramNational Institute of Biological Sciences (NIBS)National Institute of Biological Sciences (NIBS)||Graduate School of Peking Union Medical College||Chinese Institute for Brain Research||Tsinghua Institute of Multidisciplinary Biomedical Research (TIMBR)
基础医学生理学分子生物学
Wu Zhaofa,Zou Haiyue,Wu Wenting,Gao Xinwei,Wang Shu,Ren Yuqi,Weng Danwei,Guo Qingchun,Dai Ruicheng,Li Heng,Li Yulong,Qi Zhongyang,Yu Tao,Cui Yuting,Luo Minmin.A Neuropsin-based Optogenetic Tool for Precise Control of G q signaling[EB/OL].(2025-03-28)[2025-06-07].https://www.biorxiv.org/content/10.1101/2022.02.22.481462.点此复制
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