Tunable and Photoswitchable Chemically Induced Dimerization for Chemo-optogenetic Control of Protein and Organelle Positioning
Tunable and Photoswitchable Chemically Induced Dimerization for Chemo-optogenetic Control of Protein and Organelle Positioning
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DOI：
10.1002/anie.201800140
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发表时间：
2018-06-04
影响因子：
16.6
通讯作者：
Wu, Yao-Wen
中科院分区：
文献类型：
--
作者：
Chen, Xi;Wu, Yao-Wen
蛋白质和细胞器的时空动力学在控制不同的细胞过程中起着重要作用。利用光敏蛋白质和化学诱导二聚化(CID)的光遗传工具，可以控制蛋白质的二聚化，已被用于阐明生物系统的动力学和剖析复杂的生物调控网络。然而，目前的光遗传和CID系统的固有局限性仍然是在精确的时间和位置微调细胞活动的重大挑战。在这里，我们提出了一种新的化学光遗传方法，即光开关化学诱导二聚化(PsCID)，通过使用蓝光以快速和可逆的方式控制细胞功能。此外，psCID是可调的，也就是说，可以通过施加不同剂量的光照来微调二聚化和解聚程度。使用这种方法，我们可以控制活细胞中蛋白质的定位和细胞器的定位，具有很高的空间(Mum)和时间(Ms)精度。
The spatiotemporal dynamics of proteins and organelles play an important role in controlling diverse cellular processes. Optogenetic tools using photosensitive proteins and chemically induced dimerization (CID), which allow control of protein dimerization, have been used to elucidate the dynamics of biological systems and to dissect the complicated biological regulatory networks. However, the inherent limitations of current optogenetic and CID systems remain a significant challenge for the fine-tuning of cellular activity at precise times and locations. Herein, we present a novel chemo-optogenetic approach, photoswitchable chemically induced dimerization (psCID), for controlling cellular function by using blue light in a rapid and reversible manner. Moreover, psCID is tunable; that is, the dimerization and dedimerization degrees can be fine-tuned by applying different doses of illumination. Using this approach, we control the localization of proteins and positioning of organelles in live cells with high spatial (mu m) and temporal (ms) precision.