Photoswitchable diacylglycerols enable optical control of protein kinase C

James Allen Frank, Dmytro A. Yushchenko, David J. Hodson, Noa Lipstein, Jatin Nagpal, Guy A. Rutter, Jeong Seop Rhee, Alexander Gottschalk, Nils Brose, Carsten Schultz, Dirk Trauner

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Increased levels of the second messenger lipid diacylglycerol (DAG) induce downstream signaling events including the translocation of C1-domain-containing proteins toward the plasma membrane. Here, we introduce three light-sensitive DAGs, termed PhoDAGs, which feature a photoswitchable acyl chain. The PhoDAGs are inactive in the dark and promote the translocation of proteins that feature C1 domains toward the plasma membrane upon a flash of UV-A light. This effect is quickly reversed after the termination of photostimulation or by irradiation with blue light, permitting the generation of oscillation patterns. Both protein kinase C and Munc13 can thus be put under optical control. PhoDAGs control vesicle release in excitable cells, such as mouse pancreatic islets and hippocampal neurons, and modulate synaptic transmission in Caenorhabditis elegans. As such, the PhoDAGs afford an unprecedented degree of spatiotemporal control and are broadly applicable tools to study DAG signaling.

Original languageEnglish (US)
Pages (from-to)755-762
Number of pages8
JournalNature Chemical Biology
Volume12
Issue number9
DOIs
StatePublished - Sep 1 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Frank, J. A., Yushchenko, D. A., Hodson, D. J., Lipstein, N., Nagpal, J., Rutter, G. A., Rhee, J. S., Gottschalk, A., Brose, N., Schultz, C., & Trauner, D. (2016). Photoswitchable diacylglycerols enable optical control of protein kinase C. Nature Chemical Biology, 12(9), 755-762. https://doi.org/10.1038/nchembio.2141