Using a revolutionary live-cell microscopy technique, an international team of scientist has observed for the first time individual receptors for hormones and widely used drugs at work in intact cells.
G protein-coupled receptors (GPCRs) are among the "hottest” targets for the therapy of diseases such as hypertension, asthma or Parkinson´s. These receptors are the site of action of many hormones and neurotransmitters and allow them to regulate the activity of our cells. As a result, around half of all currently prescribed drugs are targeting these receptors to treat several widespread diseases.
Hot spot for receptor signalling. The cytoskeleton and other structural components of the cell membrane confine receptors and G proteins in nanodomains.
Graphic: Team Calebiro
As their name suggests, these receptors have to “find” and interact with so-called G proteins on the cell membrane in order to initiate and regulate intracellular processes. How and where this happens has long been the subject of numerous hypotheses, which, however, could never be confirmed.
An international team of scientists from the Universities of Würzburg, Birmingham and Wroclaw has now succeeded for the first time to directly observe and investigate the initial contacts between individual receptors and G proteins and the following events taking place at the surface of living cells.
Publication in Nature
"We were able to show that receptors and G proteins preferentially meet at special sites on the cell membrane, which we call hot spots", explains Professor Davide Calebiro, the senior author of the study, which has just appeared in the prestigious scientific journal Nature. Prof. Calebiro is working at the Institute of Pharmacology and Toxicology and at the Bio-Imaging Center of the University of Würzburg as well as at the Center of Membrane Proteins and Receptors of the Universities of Birmingham and Nottingham.
These detailed observations at the cell membrane of living cells were made possible by the use of a highly sophisticated method based on single-molecule microscopy. The authors also observed that receptors and G proteins usually remain associated only for a short time. Indeed, most interactions terminated after just one second. Furthermore, the researchers found that the cytoskeleton underneath the cell membrane plays an important role in the formation of the hot spots. The existence of these hot spots for receptor signaling was hitherto unknown.
Technological developments allow new insights
Davide Calebiro and his co-authors are convinced that the hot spots exert an important influence on receptor signaling by increasing both the speed and efficiency of G protein activation. At the same time, they allow the resulting signals to stay local. According to the scientists, their new findings show that "apparently simple biological processes can be highly sophisticated once observed from a short distance". They anticipate that the current “exceptional advances” in imaging techniques will lead to a much deeper understanding of these processes in the near future.
According to the authors, the newly gained insights provide the opportunity for new therapeutic approaches. "Currently used drugs can only either activate or block the receptors," explains Davide Calebiro. In the future, it might be possible to influence these processes much more precisely for example by manipulating the mobility of receptors and G proteins on the cell membrane or their interactions at the hot spots.
This study was supported by the Deutsche Forschungsgemeinschaft (DFG).
Single-molecule imaging reveals receptor-G protein interactions at cell surface hot spots. Titiwat Sungkaworn, Marie-Lise Jobin, Krzysztof Burnecki, Aleksander Weron, Martin J. Lohse & Davide Calebiro. Nature, published online 18 October 2017, doi: 10.1038 / nature24264
Prof. Dr. med. Dr. Davide Calebiro, T: +49 931 31-80067, email@example.com
Simultaneous visualization and tracking of individual receptors (green) and G proteins (magenta) at the surface of a living cell. The receptors and G proteins undergo transient interactions, which occur preferentially at “hot spots” on the cell membrane. (Video: Team Calebiro)
Gunnar Bartsch | Julius-Maximilians-Universität Würzburg
Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex
New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
22.06.2018 | Materials Sciences
22.06.2018 | Earth Sciences
22.06.2018 | Life Sciences