PhoDAGs Enable Optical Control of Diacylglycerol-Sensitive Transient Receptor Potential Channels. Issue 2 (15th February 2018)

• Record Type: Journal Article
• Authors: Leinders-Zufall, Trese; Storch, Ursula; Bleymehl, Katherin; Mederos y Schnitzler, Michael; Frank, James A.; Konrad, David B.; Trauner, Dirk; Gudermann, Thomas; Zufall, Frank
• Is Part Of: Cell chemical biology. Volume 25:Issue 2(2018)
• Page Start: 215
• Page End: 223.e3
• Publication Date: 2018-02-15
• Subjects: photopharmacology -- pheromone -- olfactory -- vomeronasal -- type B cell -- oxygen sensor -- type A cell -- cardiopulmonary function -- kidney disease -- lipid signaling; Biochemistry -- Periodicals; 572.05
• DOI: 10.1016/j.chembiol.2017.11.008
• Languages: English
• ISSNs: 2451-9456

Abstract

Summary: Diacylglycerol-sensitive transient receptor potential (TRP) channels play crucial roles in a wide variety of biological processes and systems, but their activation mechanism is not well understood. We describe an optical toolkit by which activation and deactivation of these ion channels can be controlled with unprecedented speed and precision through light stimuli. We show that the photoswitchable diacylglycerols PhoDAG-1 and PhoDAG-3 enable rapid photoactivation of two DAG-sensitive TRP channels, Trpc2 and TRPC6, upon stimulation with UV-A light, whereas exposure to blue light terminates channel activation. PhoDAG photoconversion can be applied in heterologous expression systems, in native cells, and even in mammalian tissue slices. Combined laser scanning-controlled photoswitching and Ca 2+ imaging enables both large-scale mapping of TRP channel-mediated neuronal activation and localized mapping in small cellular compartments. Light-switchable PhoDAGs provide an important advance to explore the pathophysiological relevance of DAG-sensitive TRP channels in the maintenance of body homeostasis. Graphical Abstract: Highlights: Activation mechanisms of diacylglycerol-sensitive TRP channels remain unclear Photoswitchable diacylglycerols enable high-precision gating of TRP channels All-optical stimulation and recording of TRP channels in mammalian tissue slices Light-switchable PhoDAGs are novel tools in TRP channel research Abstract : Diacylglycerol-sensitive TRP channels play important roles in health and disease, but their activation mechanisms are not well understood. Leinders-Zufall et al. develop an optical toolkit that enables monitoring of the effects of these channels with unprecedented speed and precision.