Red light-regulated reversible nuclear localization of proteins in mammalian cells and zebrafish

30.03.2015

Beyer HM, Juillot S, Herbst K, Samodelov SL, Müller K, Schamel WW, Römer W, Schäfer E, Nagy F, Strähle U, Weber W, Zurbriggen MD.

ACS Synth Biol. 2015;4(9):951-8.

ACS Synth Biol.          online article

Protein trafficking in and out of the nucleus represents a key step in controlling cell fate and function. Here we report the development of a red light-inducible and far-red light-reversible synthetic system for controlling nuclear localization of proteins in mammalian cells and zebrafish. First, we synthetically reconstructed and validated the red light-dependent Arabidopsis phytochrome B nuclear import mediated by phytochrome-interacting factor 3 in a nonplant environment and support current hypotheses on the import mechanism in planta. On the basis of this principle we next regulated nuclear import and activity of target proteins by the spatiotemporal projection of light patterns. A synthetic transcription factor was translocated into the nucleus of mammalian cells and zebrafish to drive transgene expression. These data demonstrate the first in vivo application of a plant phytochrome-based optogenetic tool in vertebrates and expand the repertoire of available light-regulated molecular devices.