The Unlimited Potential of Microbial Rhodopsins as Optical Tools
The Unlimited Potential of Microbial Rhodopsins as Optical Tools
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DOI：
10.1021/acs.biochem.9b00768
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发表时间：
2020-01-28
期刊：
影响因子：
2.9
通讯作者：
Sudo, Yuki
中科院分区：
文献类型：
--
作者：
Kojima, Keiichi;Shibukawa, Atsushi;Sudo, Yuki
微生物视紫红质是一种光活性膜蛋白家族，是光遗传学这一用光控制生物活性的创新技术的基础工具。微生物紫红质广泛分布于自然界，具有多种多样的生物学功能。尽管有许多不同类型的已知微生物视紫红质，但其中只有少数被用于光遗传学来控制神经活动以了解神经网络。我们小组的工作旨在从自然界中鉴定和表征新的视紫红质，并通过合理的设计来设计新的变异体视紫红质。根据这些新型视紫红质的分子和功能特征，我们提出了新的基于视紫红质的光遗传学工具，不仅可以控制神经活动，还可以控制“非神经”活动。在这一展望中，我们介绍了利用视紫红质创建光遗传学工具的成就，并总结了未来面临的挑战。在体内大脑深处实现光遗传学是现有视紫红质面临的众所周知的挑战。为了解决这一挑战，我们引入了利用波前整形的创新光学照明技术，该技术可以增强视紫红质的低光敏感性，并实现深部脑光遗传学。我们的光遗传学工具的应用可以扩展到操纵非神经生物活动，如基因表达、细胞凋亡、能量产生和肌肉收缩。我们还讨论了微生物紫红质在未来潜在的无限生物技术应用，如光伏器件和药物输送系统。我们相信，该领域的进展将极大地扩展微生物视紫红质作为光学工具的潜在用途。
Microbial rhodopsins, a photoactive membrane protein family, serve as fundamental tools for optogenetics, an innovative technology for controlling biological activities with light. Microbial rhodopsins are widely distributed in nature and have a wide variety of biological functions. Regardless of the many different known types of microbial rhodopsins, only a few of them have been used in optogenetics to control neural activity to understand neural networks. The efforts of our group have been aimed at identifying and characterizing novel rhodopsins from nature and also at engineering novel variant rhodopsins by rational design. On the basis of the molecular and functional characteristics of those novel rhodopsins, we have proposed new rhodopsin-based optogenetics tools to control not only neural activities but also "non-neural" activities. In this Perspective, we introduce the achievements and summarize future challenges in creating optogenetics tools using rhodopsins. The implementation of optogenetics deep inside an in vivo brain is the well-known challenge for existing rhodopsins. As a perspective to address this challenge, we introduce innovative optical illumination techniques using wavefront shaping that can reinforce the low light sensitivity of the rhodopsins and realize deep-brain optogenetics. The applications of our optogenetics tools could be extended to manipulate non-neural biological activities such as gene expression, apoptosis, energy production, and muscle contraction. We also discuss the potentially unlimited biotechnological applications of microbial rhodopsins in the future such as in photovoltaic devices and in drug delivery systems. We believe that advances in the field will greatly expand the potential uses of microbial rhodopsins as optical tools.