PhoDAGs Enable Optical Control of Diacylglycerol-Sensitive Transient Receptor Potential Channels

Trese Leinders-Zufall, Ursula Storch, Katherin Bleymehl, Michael Mederos y Schnitzler, James A. Frank, David B. Konrad, Dirk Trauner, Thomas Gudermann, Frank Zufall

Research output: Contribution to journalArticle

Abstract

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. 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.

Original languageEnglish (US)
Pages (from-to)215-223.e3
JournalCell Chemical Biology
Volume25
Issue number2
DOIs
StatePublished - Feb 15 2018

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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  • Cite this

    Leinders-Zufall, T., Storch, U., Bleymehl, K., Mederos y Schnitzler, M., Frank, J. A., Konrad, D. B., Trauner, D., Gudermann, T., & Zufall, F. (2018). PhoDAGs Enable Optical Control of Diacylglycerol-Sensitive Transient Receptor Potential Channels. Cell Chemical Biology, 25(2), 215-223.e3. https://doi.org/10.1016/j.chembiol.2017.11.008