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Molecular Switches: Light-controlled Mediators

Photoswitchable fatty acids allow the light-dependent displacement of the enzyme protein kinase C to the cell membrane. Image: D. Trauner

LMU and EMBL researchers equipped vital cellular transmitters with an optical switch. This allows them to get detailed insight into the complex communication networks of metabolism.

 

Cells respond to external stimuli and transmit signals inside further. A central switching point accepts so-called secondary transmitters such as diacylglycerols (DAG): By changing its concentration, the cell activates intracellular signaling pathways. In this way, diacylglycerols (DAG) are involved in the regulation of a number of vital metabolic processes such as the insulin secretion. A team led by Dirk Trauner, Professor of Chemical Biology and Genetics at LMU, and Carsten Schultz from the European Molecular Biology Laboratory (EMBL) in Heidelberg now found a new way to investigate the complex signaling network of transmitters in detail: They could link three of the diacylglycerols with a molecular switch that responds to light. With this construction, it is now possible to precisely control the corresponding signal paths in the experiment with UV light.

Diacylglycerols are widely used in the organism. More than 50 variants of them exist in human cells. The molecules interact with both the cell membrane as well as with soluble proteins within the cell. The photo switch built into the diacylglycerols "change their structure depending on the wavelength of light they are exposed to," says James Frank, employee in Trauners Team and author of the paper. The light-sensitive hybrid molecules are inactive in the dark and are activated by irradiation with UV light. Irradiation with blue light reverses the effect. "Interestingly, we were able to steer proteins that bind diacylglycerol with light from one location in the cell to another - simply by a flash of light," adds Carsten Schultz. The three Diacylyglycerides which have been reshaped by Trauners team, engage in important metabolic processes, including hormone secretion from the pancreas and signal transmission between nerve cells. The researchers were able to control these processes in the experiment with light. "In the model organism Caenorhabditis elegans, a small nematode, we could see the stimulus transmission to neuromuscular junctions even increase in vivo by UV light," says Trauner.
Nature Chemical Biology 2016