Department of Chemistry, Ludwig-Maximilians-Universität and Center for Integrated Protein Science, 81377 Munich, Germany.
Angew Chem Int Ed Engl. 2011 Dec 16;50(51):12156-82. doi: 10.1002/anie.201103236. Epub 2011 Nov 23.
Transmembrane receptors allow a cell to communicate with its environment in response to a variety of input signals. These can be changes in the concentration of ligands (e.g. hormones or neurotransmitters), temperature, pressure (e.g. acoustic waves or touch), transmembrane potential, or light intensity. Many important receptors have now been characterized in atomic detail and our understanding of their functional properties has markedly increased in recent years. As a consequence, these sophisticated molecular machines can be reprogrammed to respond to unnatural input signals. In this Review, we show how voltage-gated and ligand-gated ion channels can be endowed with synthetic photoswitches, and how the resulting artificial photoreceptors can be used to optically control neurons with exceptional temporal and spatial precision. They work well in animals and might find applications in the restoration of vision and the optical control of other sensations. The combination of synthetic photoswitches and receptor proteins contributes to the field of optogenetics and adds a new functional dimension to chemical genetics. As such, we propose to call it "optochemical genetics".
跨膜受体允许细胞根据各种输入信号与其环境进行通讯。这些输入信号可以是配体(如激素或神经递质)浓度、温度、压力(如声波或触觉)、跨膜电位或光强度的变化。现在已经对许多重要的受体进行了原子细节的描述,并且近年来我们对它们的功能特性的理解有了显著提高。因此,这些复杂的分子机器可以被重新编程以响应非自然输入信号。在这篇综述中,我们展示了如何赋予电压门控和配体门控离子通道合成光开关,以及如何使用由此产生的人工光感受器以极高的时间和空间精度对神经元进行光学控制。它们在动物中效果良好,可能在视力恢复和其他感觉的光学控制方面有应用。合成光开关和受体蛋白的结合促进了光遗传学领域的发展,并为化学生物学增加了一个新的功能维度。因此,我们建议将其称为“光化学生物学”。