Chemical Genomics Centre of the Max Planck Society, Otto-Hahn-Str. 15, 44227, Dortmund, Germany.
Max Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227, Dortmund, Germany.
Angew Chem Int Ed Engl. 2018 Jun 4;57(23):6796-6799. doi: 10.1002/anie.201800140. Epub 2018 May 8.
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 (μm) and temporal (ms) precision.
蛋白质和细胞器的时空动态在控制多种细胞过程中起着重要作用。光遗传学工具利用光敏蛋白和化学诱导二聚体（CID），可以控制蛋白质二聚体的形成，从而用于阐明生物系统的动态，并剖析复杂的生物调控网络。然而，当前光遗传学和 CID 系统的固有局限性仍然是在精确的时间和位置上精细调节细胞活性的重大挑战。在此，我们提出了一种新的化学光遗传学方法，即光可切换化学诱导二聚体（psCID），用于通过快速和可逆的蓝光控制细胞功能。此外，psCID 是可调的；也就是说，通过施加不同剂量的光照，可以精细调节二聚体和解二聚体的程度。使用这种方法，我们可以以高空间（μm）和时间（ms）精度控制活细胞中蛋白质的定位和细胞器的定位。
