Synthetic Physiology, Institute of Science and Technology Austria (IST Austria), Am Campus 1, 3400, Klosterneuburg, Austria.
Innovative Cancer Models, Children's Cancer Research Institute (CCRI), Zimmermannplatz 10, 1090, Vienna, Austria.
Angew Chem Int Ed Engl. 2017 Apr 10;56(16):4608-4611. doi: 10.1002/anie.201611998. Epub 2017 Mar 20.
Optogenetics and photopharmacology provide spatiotemporally precise control over protein interactions and protein function in cells and animals. Optogenetic methods that are sensitive to green light and can be used to break protein complexes are not broadly available but would enable multichromatic experiments with previously inaccessible biological targets. Herein, we repurposed cobalamin (vitamin B12) binding domains of bacterial CarH transcription factors for green-light-induced receptor dissociation. In cultured cells, we observed oligomerization-induced cell signaling for the fibroblast growth factor receptor 1 fused to cobalamin-binding domains in the dark that was rapidly eliminated upon illumination. In zebrafish embryos expressing fusion receptors, green light endowed control over aberrant fibroblast growth factor signaling during development. Green-light-induced domain dissociation and light-inactivated receptors will critically expand the optogenetic toolbox for control of biological processes.
光遗传学和光药理学提供了在细胞和动物中对蛋白质相互作用和蛋白质功能进行时空精确控制的手段。对绿光敏感且可用于打破蛋白质复合物的光遗传学方法尚未广泛应用，但将使以前无法触及的生物靶标进行多色实验成为可能。在此，我们重新设计了细菌 CarH 转录因子的钴胺素（维生素 B12）结合域，用于绿光诱导的受体解离。在培养的细胞中，我们观察到与融合到钴胺素结合域的成纤维细胞生长因子受体 1 寡聚化诱导的细胞信号在黑暗中发生，而在光照下迅速消除。在表达融合受体的斑马鱼胚胎中，绿光赋予了对发育过程中异常成纤维细胞生长因子信号的控制。绿光诱导的结构域解离和光失活的受体将极大地扩展光遗传学工具包，以控制生物过程。
