A phytochrome sensory domain permits receptor activation by red light Journal Article

Author(s): Reichhart, Eva; Ingles-Prieto, Álvaro; Tichy, Alexandra-Madelaine; McKenzie, Catherine; Janovjak, Harald
Article Title: A phytochrome sensory domain permits receptor activation by red light
Affiliation IST Austria
Abstract: 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.
Keywords: Optogenetics; receptors; photochromism; phytochrome
Journal Title: Angewandte Chemie - International Edition
Volume: 55
Issue 21
ISSN: 1521-3773
Publisher: Wiley-Blackwell  
Date Published: 2016-05-17
Start Page: 6339
End Page: 6342
DOI: 10.1002/anie.201601736
Notes: We thank M. Spanova and K. Kolev for technical assistance, R. Riedler, S. Laukoter, and S. zur Nedden for help with initial experiments, P. Maechler for INS-1E cells, I. Maldener for cyanobacteria, R. Y. Tsien for mCherry and mVenus, M. Davidson for mCerulean3, and M. Grusch for discussions. This work was supported by EU FP7 (CIG-303564). 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).
Open access: yes (repository)