Cell Chemical Biology
Volume 25, Issue 2, 15 February 2018, Pages 215-223.e3
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PhoDAGs Enable Optical Control of Diacylglycerol-Sensitive Transient Receptor Potential Channels

https://doi.org/10.1016/j.chembiol.2017.11.008Get rights and content
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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

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 Ca2+ 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.

Keywords

photopharmacology
pheromone
olfactory
vomeronasal
type B cell
oxygen sensor
type A cell
cardiopulmonary function
kidney disease
lipid signaling

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