Deisseroth Karl, Hegemann Peter
Department of Bioengineering, Stanford University, Stanford, CA, USA.
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Science. 2017 Sep 15;357(6356). doi: 10.1126/science.aan5544.
Channelrhodopsins are light-gated ion channels that, via regulation of flagellar function, enable single-celled motile algae to seek ambient light conditions suitable for photosynthesis and survival. These plant behavioral responses were initially investigated more than 150 years ago. Recently, major principles of function for light-gated ion channels have been elucidated by creating channelrhodopsins with kinetics that are accelerated or slowed over orders of magnitude, by discovering and designing channelrhodopsins with altered spectral properties, by solving the high-resolution channelrhodopsin crystal structure, and by structural model-guided redesign of channelrhodopsins for altered ion selectivity. Each of these discoveries not only revealed basic principles governing the operation of light-gated ion channels, but also enabled the creation of new proteins for illuminating, via optogenetics, the fundamentals of brain function.
视紫红质通道蛋白是光门控离子通道,通过调节鞭毛功能,使单细胞运动藻类能够寻找适合光合作用和生存的环境光照条件。这些植物行为反应最初是在150多年前进行研究的。最近,通过创建动力学在多个数量级上加速或减慢的视紫红质通道蛋白,发现和设计具有改变光谱特性的视紫红质通道蛋白,解析视紫红质通道蛋白的高分辨率晶体结构,以及通过结构模型指导对视紫红质通道蛋白进行重新设计以改变离子选择性,光门控离子通道的主要功能原理已得到阐明。这些发现中的每一个不仅揭示了光门控离子通道运作的基本原理,还通过光遗传学创造了用于阐明脑功能基本原理的新蛋白质。