Scientists have developed new technology to study important receptors

Adhesion GPCRs are a group of G protein-coupled receptors involved in many body functions and diseases. However, they have not been studied enough to be used for therapies. Two research groups at the Rudolf Schönheimer Institute of the Faculty of Medicine at Leipzig University are now jointly developing a technology to change this.

The novel NRS (NTF Release Sensor) technique captures unique molecular switch events in adhesion GPCRs that were previously hidden from researchers. These important findings were recently published in the NATURE.

About 40 percent of all drugs act on G protein-coupled receptors (GPCRs), which provide relief or even cures for various diseases. These include compounds used to treat Parkinson’s disease, pain, high blood pressure and allergies. GPCRs are easily accessible to drugs because they are located on the surface of cells. In addition, each cell in the body and its organs have specific GPCR patterns, which means that the effects of GPCR drugs can be limited.

“However, a large family within the more than 700 member GPCR class, the adhesion GPCRs (aGPCRs), is still uncharted pharmacological and pharmaceutical territory. These molecules are involved in a wide variety of diseases, from cancer to psychiatric disorders,” explained Dr. Nicole Scholz, group leader of the Chair of General Biochemistry at the Rudolf Schönheimer Institute and one of the two leaders of the new study.

Adhesion GPCRs are a large class of surface proteins that recognize chemical and mechanical stimuli in the body. They have not been exploited for therapeutic drugs. aGPCRs have a two-part structure and a unique activation mechanism. Scientists from Leipzig now present a molecular sensor system that can be used in living organisms and in cell culture dishes to detect when and where an aGPCR breaks down as a result of mechanical stimulation, thus separating the two components.

This break activates receptors and thus plays an important role in the transmission of biochemical signals. Dr. Scholz and Professor Langenhan filed a patent application for this technology in close collaboration with the Technology Transfer Office of Leipzig University. The goal is to provide legal protection for new findings and to help bring the methods currently available for aGPCR drug identification to the point of practical use.

“There is an idea that many aGPCRs are activated like hand grenades. The two parts of the aGPCR are like the safety pin and the explosive charge. the shape of the activity of the receptor. Through our work, we can now will offer a method to see this mechanism. In particular, we were able to show where the separation of the receptor cells took place and under what conditions,” said Tobias Langenhan, Professor of the General. Biochemistry at the Rudolf Schönheimer Institute and co-leader of the study with Dr. Scholz.

Dr. Scholz added, “We succeeded in visualizing an important biological process in a large receptor family in a living animal, the fruit fly. Future projects will include the translation of these findings to human aGPCRs. In the best case scenario, in the long term, we will be able to find compounds that modulate the activity of these receptors, and to develop drugs that can cure the symptoms of adhesion GPCR-related diseases.”