Photoswitchable diacylglycerols enable optical control of protein kinase C

Research output: Contribution to journalArticle

Authors

  • James Frank
  • Dmytro Yushchenko
  • Noa Lipstein
  • Jatin Nagpal
  • Guy Rutter
  • Jeong-Seop Rhee
  • Alexander Gottschalk
  • Nils Brose
  • Carsten Schultz
  • Dirk Trauner

Colleges, School and Institutes

External organisations

  • LMU Munich; Department of Chemistry and Center for Integrated Protein Science (CIPSM); Butenandtstrasse 5-13 81377 Munich Germany
  • Europ. Molecular Biology Laboratory
  • Dept of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Gottingen, Germany
  • Buchmann Institute for Molecular Life Sciences (BMLS)
  • Imperial College London

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 allowing for reversible isomerization under the control of light. The PhoDAGs are inactive in the dark and promote the translocation of proteins that feature C1 domains towards the plasma membrane upon stimulation with UV-A irradiation. 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.

Details

Original languageEnglish
Pages (from-to)755-762
JournalNature Chemical Biology
Volume12
Publication statusPublished - 25 Jul 2016