Frank James Allen, Yushchenko Dmytro A, Hodson David J, Lipstein Noa, Nagpal Jatin, Rutter Guy A, Rhee Jeong-Seop, Gottschalk Alexander, Brose Nils, Schultz Carsten, Trauner Dirk
Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Munich, Germany.
Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
Nat Chem Biol. 2016 Sep;12(9):755-62. doi: 10.1038/nchembio.2141. Epub 2016 Jul 25.
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.
第二信使脂质二酰甘油（DAG）水平的升高会引发下游信号事件，包括含C1结构域的蛋白质向质膜的转位。在此，我们引入了三种光敏感的DAG，称为PhoDAG，其具有可光开关的酰基链。PhoDAG在黑暗中无活性，在紫外-A光照射后可促进具有C1结构域的蛋白质向质膜转位。在光刺激终止后或通过蓝光照射，这种效应会迅速逆转，从而产生振荡模式。因此，蛋白激酶C和Munc13都可以置于光学控制之下。PhoDAG可控制可兴奋细胞（如小鼠胰岛和海马神经元）中的囊泡释放，并调节秀丽隐杆线虫中的突触传递。因此，PhoDAG提供了前所未有的时空控制程度，是研究DAG信号传导的广泛适用工具。
