PhoDAGs Enable Optical Control of Diacylglycerol-Sensitive Transient Receptor Potential Channels
PhoDAGs Enable Optical Control of Diacylglycerol-Sensitive Transient Receptor Potential Channels
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DOI：
10.1016/j.chembiol.2017.11.008
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发表时间：
2018-02-15
影响因子：
8.6
通讯作者：
Zufall, Frank
中科院分区：
文献类型：
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作者：
Leinders-Zufall, Trese;Storch, Ursula;Zufall, Frank
二酰基甘油敏感性瞬时受体电位（TRP）通道在多种生物过程和系统中发挥着重要作用，但其激活机制尚不清楚。我们描述了一个光学工具包，通过它可以通过光刺激以前所未有的速度和精度控制这些离子通道的激活和失活。我们表明，光开关二酰基甘油PhoDAG-1和PhoDAG-3，使两个DAG敏感的TRP通道，Trpc 2和TRPC 6，在用UV-A光刺激后快速光活化，而暴露于蓝光终止通道激活。PhoDAG光转化可应用于异源表达系统、天然细胞、甚至哺乳动物组织切片中。结合激光扫描控制的光开关和Ca 2+成像，使大规模映射TRP通道介导的神经元激活和局部映射在小细胞室。光可切换的PhoDAGs为探索DAG敏感的TRP通道在维持体内稳态中的病理生理学相关性提供了重要进展。
Diacylglycerol-sensitive transient receptor potential (TRP) channels play crucial roles in a wide variety of biological processes and systems, but their activation mechanism is not well understood. We describe an optical toolkit by which activation and deactivation of these ion channels can be controlled with unprecedented speed and precision through light stimuli. We show that the photoswitchable diacylglycerols PhoDAG-1 and PhoDAG-3 enable rapid photoactivation of two DAG-sensitive TRP channels, Trpc2 and TRPC6, upon stimulation with UV-A light, whereas exposure to blue light terminates channel activation. PhoDAG photoconversion can be applied in heterologous expression systems, in native cells, and even in mammalian tissue slices. Combined laser scanning-controlled photoswitching and Ca2+ imaging enables both large-scale mapping of TRP channel-mediated neuronal activation and localized mapping in small cellular compartments. Light-switchable PhoDAGs provide an important advance to explore the pathophysiological relevance of DAG-sensitive TRP channels in the maintenance of body homeostasis.