Graduate School of Science, Tohoku University, Sendai, Japan.
Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan.
Nat Chem Biol. 2024 Nov;20(11):1461-1470. doi: 10.1038/s41589-024-01654-w. Epub 2024 Jun 18.
Artificial control of intracellular protein dynamics with high precision provides deep insight into complicated biomolecular networks. Optogenetics and caged compound-based chemically induced dimerization (CID) systems are emerging as tools for spatiotemporally regulating intracellular protein dynamics. However, both technologies face several challenges for accurate control such as the duration of activation, deactivation rate and repetition cycles. Herein, we report a photochromic CID system that uses the photoisomerization of a ligand so that both association and dissociation are controlled by light, enabling quick, repetitive and quantitative regulation of the target protein localization upon illumination with violet and green light. We also demonstrate the usability of the photochromic CID system as a potential tool to finely manipulate intracellular protein dynamics during multicolor fluorescence imaging to study diverse cellular processes. We use this system to manipulate PTEN-induced kinase 1 (PINK1)-Parkin-mediated mitophagy, showing that PINK1 recruitment to the mitochondria can promote Parkin recruitment to proceed with mitophagy.
利用高精度的人工控制细胞内蛋白质动力学为复杂的生物分子网络提供了深入的见解。光遗传学和基于笼状化合物的化学诱导二聚（CID）系统正在成为时空调节细胞内蛋白质动力学的工具。然而，这两种技术在精确控制方面都面临着一些挑战，例如激活持续时间、失活速率和重复周期。在此，我们报告了一种光致变色 CID 系统，该系统利用配体的光致异构化，使结合和解离都受到光的控制，从而可以在紫光和绿光照射下快速、重复和定量地调节靶蛋白的定位。我们还证明了光致变色 CID 系统作为一种潜在工具的可用性，可在多色荧光成像过程中精细地操纵细胞内蛋白质动力学，以研究各种细胞过程。我们使用该系统来操纵 PTEN 诱导的激酶 1（PINK1）-Parkin 介导的线粒体自噬，表明 PINK1 向线粒体的募集可以促进 Parkin 的募集以进行线粒体自噬。
