Whether our heart beats properly depends on tiny receptors in our cells. These so-called receptors receive signals from outside and transmit them. Until now, they were thought to function like simple light switches. But researchers at Leipzig University have now shown: The reality is much more complex. This opens up new opportunities for better drugs.
The team led by Prof. Irene Coin and Prof. Andreas Bock from the Collaborative Research Center 1423 has observed for the first time in living cells how an important membrane receptor works. This so-called M2 receptor regulates our heart function, among other things. The scientists were able to show that Depending on which active substance docks to the receptor, it takes on different forms and works at different speeds. This influences which signals are passed on in the cell.
Luminous molecules as scouts
The special thing about this is an idea from the Leipzig team. "We have developed a new type of biosensor in which tiny luminescent molecules are attached directly to the receptors in living cells," explains Irene Coin. Previously, larger luminescent proteins were used for this purpose, but they were too coarse to detect subtle changes.
The researchers are now incorporating artificial building blocks into the receptor. They then attach the luminescent molecules to these. As soon as the receptor becomes active, the light changes. This allows the scientists to observe in real time how individual parts of the receptor move.
Hope for drugs without side effects
The findings are particularly important because around a third of all drugs act on such receptors. They belong to the large group of so-called G protein-coupled receptors, or GPCRs for short. "We expect that similar activation processes also occur in many other receptors. Our biosensors could help to find active substances that act precisely on certain signaling pathways in the cell or preferentially activate certain G-proteins," says Coin.
The method can also be transferred to other receptors. This could revolutionize the development of drugs. Because if you understand exactly how active substances trigger different signaling pathways, you can specifically develop those that only have the desired effects. Irene Coin emphasizes that other biosensors have already been established in the Leipzig laboratories and that research is continuing.
