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.

Buchmann Institute for Molecular Life Sciences Goethe University Frankfurt Germany

Cell Biology and Biophysics Unit European Molecular Biology Laboratory Heidelberg Germany

Centre for Endocrinology Diabetes and Metabolism Birmingham Health Partners Birmingham UK

Department of Chemistry and Center for Integrated Protein Science Ludwig Maximilians University Munich Munich Germany

Department of Molecular Neurobiology Max Planck Institute of Experimental Medicine Göttingen Germany

Institute of Biochemistry Department for Biochemistry Chemistry and Pharmacy Goethe University Frankfurt Germany

Institute of Metabolism and Systems Research University of Birmingham Birmingham UK

Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic Prague Czech Republic

Section of Cell Biology and Functional Genomics Department of Medicine Imperial College London ICTEM Hammersmith Hospital London UK

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Optical control of GPR40 signalling in pancreatic β-cells

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PubChem-Substance
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