Sensor Indicates if G-Protein-Coupled Signaling Pathway is Activated in Neural Cells

Melanospin is a G-protein-coupled receptor that governs specific signaling pathways in neural cells. In earlier studies, researchers in the Department of General Zoology and Neurobiology at Ruhr-University Bochum used the receptor as an optogenetic tool. By modifying the receptor, the scientists were able to switch it on with blue light and off with yellow light. Thus, they could activate various G-protein-coupled signaling pathways in neural cells using light.

In the current study, the team optimized the tool and turned it into a sensor that indicates if a G-protein-coupled signaling pathway has been switched on. Once such a signaling pathway is activated, the concentration of calcium ions in the cell increases. The researchers melded melanopsin with a calcium indicator protein, whose fluorescence intensity increases following a surge in calcium concentration in the cell. Green light thus indicated that a G-protein-coupled signaling pathway had been activated.

Subsequently, the biologists added two more functions to their sensor—the calcium-melanopsin-local-sensor (Camello). They integrated a second fluorescent protein that permanently emits red fluorescence. Monitoring the red light, they were able to pinpoint the sensor in the cells, regardless if a signaling pathway was switched on or not. A red light thus indicated that the Camello sensor was present, whereas an additional green light showed that it had activated signaling pathways.

“Since serotonin is involved in numerous processes in the central nervous system, it also plays an important role in many disorders, such as depression, schizophrenia, anxiety, and migraine. We are hoping that, by facilitating detailed research into the transport, localization, and activity of relevant receptors, our tool will help us understand the mechanisms underlying these diseases,” said researcher Dennis Eickelbeck.

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