期刊
NATURE CHEMICAL BIOLOGY
卷 12, 期 9, 页码 755-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nchembio.2141
关键词
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资金
- Deutsche Forschungsgemeinschaft (DFG) [SFB 1032, TRR 152]
- European Research Council (ERC) [268795]
- DFG [TRR 83, TRR 186, FOR1279 GO1011/4-1, GO1011/4-2]
- EIPOD Programme at EMBL
- EU [229597]
- IOCB installation grant
- Diabetes UK RD Lawrence [12/0004431]
- EFSD/Novo Nordisk Rising Star and Birmingham fellowships
- MRC [MR/N00275X/1]
- Imperial Confidence in Concept (ICiC) grants
- Wellcome Trust [WT098424AIA]
- Royal Society Wolfson Research Merit awards
- UK Medical Research Council [MR/J0003042/1, MR/L020149/1, MR/L02036X/1]
- Biological and Biotechnology Research Council [BB/J015873/1]
- Diabetes UK [11/0004210, 15/0005275]
- Cluster of Excellence Frankfurt [EXC115]
- BBSRC [BB/J015873/1] Funding Source: UKRI
- MRC [MR/N00275X/1, MR/L020149/1, MC_PC_14100] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/J015873/1] Funding Source: researchfish
- Medical Research Council [MR/N00275X/1, MC_PC_14100, MR/L020149/1] Funding Source: researchfish
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.
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