Blue-Light Receptors for Optogenetics.

Blue-Light Receptors for Optogenetics.
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光遗传学的蓝光受体。

DOI:
10.1021/acs.chemrev.8b00163
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发表时间:
2018-11-14
期刊:
影响因子:
62.1
通讯作者:
Möglich A
Möglich A
中科院分区:
化学1区
文献类型:
--
作者:
Losi A;Gardner KH;Möglich A

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感觉光感受器支持自然界中生物生理学、发育和行为的光依赖适应。适用于光遗传学,感觉光感受器成为基因编码的致动器和报告器,以实现细胞过程的光的非侵入性,时空准确和可逆的控制。植根于对天然光感受器的机械理解,具有定制光门控功能的人工光感受器已经被设计出来,大大扩展了光遗传学的范围,超越了光控离子流的原始应用。正如我们目前所调查的,UV/蓝光敏感的光感受器特别允许光遗传学超越其最初的神经科学应用,通过解锁许多额外的细胞过程和参数进行光遗传学干预,包括基因表达,DNA重组,亚细胞定位,细胞骨架动力学,细胞内蛋白质稳定性,信号转导级联,细胞凋亡和酶活性。新型光感受器的工程设计得益于强大且可重复使用的设计策略,最重要的是光依赖性蛋白质缔合和(非)折叠反应。此外,这些相同的感觉光感受器的修饰版本用作荧光蛋白和单线态氧的发生器,从而进一步丰富了光遗传学工具包。可用和即将推出的紫外/蓝光敏感致动器和报告器能够以越来越精确和具有启发性的方式详细和定量地询问细胞信号网络和过程。
Sensory photoreceptors underpin light-dependent adaptations of organismal physiology, development and behavior in nature. Adapted for optogenetics, sensory photoreceptors become genetically-encoded actuators and reporters to enable the non-invasive, spatiotemporally accurate and reversible control by light of cellular processes. Rooted in a mechanistic understanding of natural photoreceptors, artificial photoreceptors with customized light-gated function have been engineered that greatly expand the scope of optogenetics beyond the original application of light-controlled ion flow. As we survey presently, UV/blue-light-sensitive photoreceptors have particularly allowed optogenetics to transcend its initial neuroscience applications by unlocking numerous additional cellular processes and parameters for optogenetic intervention, including gene expression, DNA recombination, subcellular localization, cytoskeleton dynamics, intracellular protein stability, signal transduction cascades, apoptosis and enzyme activity. The engineering of novel photoreceptors benefits from powerful and reusable design strategies, most importantly light-dependent protein association and (un)folding reactions. Additionally, modified versions of these same sensory photoreceptors serve as fluorescent proteins and generators of singlet oxygen, thereby further enriching the optogenetic toolkit. The available and upcoming UV/blue-light-sensitive actuators and reporters enable the detailed and quantitative interrogation of cellular signal networks and processes in increasingly more precise and illuminating manners.
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