title: Photoswitchable diacylglycerols enable optical control of protein kinase C.
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.
authors.affiliation: Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Munich, Germany.
authors.forename: James Allen
authors.initials: JA
authors.lastname: Frank
authors.affiliation: Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.|Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Dmytro A
authors.initials: DA
authors.lastname: Yushchenko
authors.affiliation: Section of Cell Biology and Functional Genomics, Department of Medicine, Imperial College London, ICTEM, Hammersmith Hospital, London, UK.|Institute of Metabolism and Systems Research (IMSR) and Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham, UK.|Centre for Endocrinology, Diabetes and Metabolism (CEDAM), Birmingham Health Partners, Birmingham, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hodson
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Noa
authors.initials: N
authors.lastname: Lipstein
authors.affiliation: Buchmann Institute for Molecular Life Sciences, Goethe University, Frankfurt, Germany.|Institute of Biochemistry, Department for Biochemistry, Chemistry and Pharmacy, Goethe University, Frankfurt, Germany.
authors.forename: Jatin
authors.initials: J
authors.lastname: Nagpal
authors.affiliation: Section of Cell Biology and Functional Genomics, Department of Medicine, Imperial College London, ICTEM, Hammersmith Hospital, London, UK.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rutter
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Jeong-Seop
authors.initials: JS
authors.lastname: Rhee
authors.affiliation: Buchmann Institute for Molecular Life Sciences, Goethe University, Frankfurt, Germany.|Institute of Biochemistry, Department for Biochemistry, Chemistry and Pharmacy, Goethe University, Frankfurt, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gottschalk
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.affiliation: Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schultz
authors.affiliation: Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Munich, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Trauner
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects; D004075:Diglycerides / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects*; D051379:Mice; D055620:Optical Phenomena; D055668:Photochemical Processes / Q000528:radiation effects*; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects*; D015398:Signal Transduction / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: C011439:1,2-diacylglycerol; D004075:Diglycerides; D011493:Protein Kinase C