title: Optogenetic control of signaling in mammalian cells.
abstract: Molecular signals are sensed by their respective receptors and information is transmitted and processed by a sophisticated intracellular network controlling various biological functions. Optogenetic tools allow the targeting of specific signaling nodes for a precise spatiotemporal control of downstream effects. These tools are based on photoreceptors such as phytochrome B (PhyB), cryptochrome 2, or light-oxygen-voltage-sensing domains that reversibly bind to specific interaction partners in a light-dependent manner. Fusions of a protein of interest to the photoreceptor or their interaction partners may enable the control of the protein function by light-mediated dimerization, a change of subcellular localization, or due to photocaging/-uncaging of effectors. In this review, we summarize the photoreceptors and the light-based mechanisms utilized for the modulation of signaling events in mammalian cells focusing on non-neuronal applications. We discuss in detail optogenetic tools and approaches applied to control signaling events mediated by second messengers, Rho GTPases and growth factor-triggered signaling cascades namely the RAS/RAF and phosphatidylinositol-3-kinase pathways. Applying the latest generation of optogenetic tools allows to control cell fate decisions such as proliferation and differentiation or to deliver therapeutic substances in a spatiotemporally controlled manner.
authors.affiliation: Faculty of Biology, University of Freiburg, Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany.
authors.forename: Hannes M
authors.initials: HM
authors.lastname: Beyer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Naumann
authors.forename: Wilfried
authors.initials: W
authors.lastname: Weber
authors.forename: Gerald
authors.initials: G
authors.lastname: Radziwill
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D056931:Cryptochromes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D062308:Optogenetics / Q000379:methods*; D010786:Photoreceptor Cells / Q000737:chemistry* / Q000378:metabolism*; D051939:Phytochrome B / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D056931:Cryptochromes; D051939:Phytochrome B
keywords: Cryptochrome 2; Light-oxygen-voltage domains; Optogenetics; Phytochrome B; RAF/MEK/ERK pathway