Optogenetics and photopharmacology enable the spatio-temporal control of cell and animal behavior by light. Although red light offers deep-tissue penetration and minimal phototoxicity, very few red-light-sensitive optogenetic methods are currently available. We have now developed a red-light-induced homodimerization domain. We first showed that an optimized sensory domain of the cyanobacterial phytochrome 1 can be expressed robustly and without cytotoxicity in human cells. We then applied this domain to induce the dimerization of two receptor tyrosine kinases—the fibroblast growth factor receptor 1 and the neurotrophin receptor trkB. This new optogenetic method was then used to activate the MAPK/ERK pathway non-invasively in mammalian tissue and in multicolor cell-signaling experiments. The light-controlled dimerizer and red-light-activated receptor tyrosine kinases will prove useful to regulate a variety of cellular processes with light. Go deep with red: The sensory domain (S) of the cyanobacterial phytochrome 1 (CPH1) was repurposed to induce the homodimerization of proteins in living cells by red light. By using this domain, light-activated protein kinases were engineered that can be activated orthogonally from many fluorescent proteins and through mammalian tissue. Pr/Pfr=red-/far-red-absorbing state of CPH1.
Angewandte Chemie - International Edition
A.I.-P. was supported by a Ramon Areces fellowship, and E.R. by the graduate program MolecularDrugTargets (Austrian Science Fund (FWF): W1232) and a FemTech fellowship (Austrian Research Promotion Agency: 3580812).
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Gschaider-Reichhart E, Inglés Prieto Á, Tichy A-M, Mckenzie C, Janovjak HL. A phytochrome sensory domain permits receptor activation by red light. Angewandte Chemie - International Edition. 2016;55(21):6339-6342. doi:10.1002/anie.201601736
Gschaider-Reichhart, E., Inglés Prieto, Á., Tichy, A.-M., Mckenzie, C., & Janovjak, H. L. (2016). A phytochrome sensory domain permits receptor activation by red light. Angewandte Chemie - International Edition, 55(21), 6339–6342. https://doi.org/10.1002/anie.201601736
Gschaider-Reichhart, Eva, Álvaro Inglés Prieto, Alexandra-Madelaine Tichy, Catherine Mckenzie, and Harald L Janovjak. “A Phytochrome Sensory Domain Permits Receptor Activation by Red Light.” Angewandte Chemie - International Edition 55, no. 21 (2016): 6339–42. https://doi.org/10.1002/anie.201601736.
E. Gschaider-Reichhart, Á. Inglés Prieto, A.-M. Tichy, C. Mckenzie, and H. L. Janovjak, “A phytochrome sensory domain permits receptor activation by red light,” Angewandte Chemie - International Edition, vol. 55, no. 21, pp. 6339–6342, 2016.
Gschaider-Reichhart E, Inglés Prieto Á, Tichy A-M, Mckenzie C, Janovjak HL. 2016. A phytochrome sensory domain permits receptor activation by red light. Angewandte Chemie - International Edition. 55(21), 6339–6342.
Gschaider-Reichhart, Eva, et al. “A Phytochrome Sensory Domain Permits Receptor Activation by Red Light.” Angewandte Chemie - International Edition, vol. 55, no. 21, Wiley, 2016, pp. 6339–42, doi:10.1002/anie.201601736.
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