Repina Nicole A, Rosenbloom Alyssa, Mukherjee Abhirup, Schaffer David V, Kane Ravi S
Department of Bioengineering, University of California, Berkeley, California 94720; email:
Graduate Program in Bioengineering, University of California, San Francisco, and University of California, Berkeley, California 94720; email:
Annu Rev Chem Biomol Eng. 2017 Jun 7;8:13-39. doi: 10.1146/annurev-chembioeng-060816-101254.
Cells are bombarded by extrinsic signals that dynamically change in time and space. Such dynamic variations can exert profound effects on behaviors, including cellular signaling, organismal development, stem cell differentiation, normal tissue function, and disease processes such as cancer. Although classical genetic tools are well suited to introduce binary perturbations, new approaches have been necessary to investigate how dynamic signal variation may regulate cell behavior. This fundamental question is increasingly being addressed with optogenetics, a field focused on engineering and harnessing light-sensitive proteins to interface with cellular signaling pathways. Channelrhodopsins initially defined optogenetics; however, through recent use of light-responsive proteins with myriad spectral and functional properties, practical applications of optogenetics currently encompass cell signaling, subcellular localization, and gene regulation. Now, important questions regarding signal integration within branch points of signaling networks, asymmetric cell responses to spatially restricted signals, and effects of signal dosage versus duration can be addressed. This review summarizes emerging technologies and applications within the expanding field of optogenetics.
细胞受到在时间和空间上动态变化的外在信号的轰击。这种动态变化会对细胞行为产生深远影响，包括细胞信号传导、机体发育、干细胞分化、正常组织功能以及诸如癌症等疾病过程。尽管经典遗传学工具非常适合引入二元扰动，但仍需要新的方法来研究动态信号变化如何调节细胞行为。这个基本问题越来越多地通过光遗传学来解决，光遗传学是一个专注于工程和利用光敏蛋白与细胞信号通路相互作用的领域。视紫红质最初定义了光遗传学；然而，通过最近使用具有多种光谱和功能特性的光响应蛋白，光遗传学的实际应用目前涵盖了细胞信号传导、亚细胞定位和基因调控。现在，可以解决有关信号网络分支点内信号整合、细胞对空间受限信号的不对称反应以及信号剂量与持续时间的影响等重要问题。本综述总结了光遗传学不断扩展领域内的新兴技术和应用。
