Malformed desmin proteins aggregate with intact proteins of the same kind, thereby triggering skeletal and cardiac muscle diseases, the desminopathies. This was discovered by researchers from the RUB Heart and Diabetes Center NRW in Bad Oeynhausen led by PD Dr. Hendrik Milting in an interdisciplinary research project with colleagues from the universities in Karlsruhe, Würzburg and Bielefeld. They report in the Journal of Biological Chemistry.
Using Photo Activation Localization Microscopy (PALM), ten times the resolution (right) of conventional light microscopy (left) is achieved. The image shows a desmin filament which was taken with a conventional microscope and with the high-resolution PALM microscope. Illustration: Andreas Brodehl/Per Niklas Hedde
One defective gene is enough
Desmin normally forms stabilizing filaments inside of the cells. Different mutations in the DES gene, which contains the blueprint for the protein, induce different muscle diseases. Since chromosomes are always present in pairs, each cell has two DES genes on two different chromosomes. The desminopathies break out even if only one of the DES genes is mutated. With Photo Activation Localization Microscopy (PALM), the interdisciplinary team led by Dr. Milting revealed the mechanism behind this.
Making mutated and intact proteins visible
If one DES gene is mutated and one intact, a cell produces both malformed and normal proteins. Since not only the mutant desmin proteins clump together, but also the intact exemplars are incorporated into the aggregates, one defective DES gene is enough to trigger the disease. Using the PALM microscope, the researchers attach two different fluorescent molecules to the mutant and the intact proteins. They can turn these markers on and off by laser, effectively flashing them. From the “snapshots” of the intact and the mutated proteins, the computer then calculates a joint picture on which both protein variants can be seen. PALM is a novel microscopy technique that can achieve ten times higher resolution than conventional light microscopy.
Further research projects
In the next step, the research group would like to find out how mutations in the DES gene trigger what is termed arrhythmogenic right ventricular cardiomyopathy, ARVC for short. This rare heart muscle disease is characterized by a severe defect – especially to the right ventricle – and by heart rhythm problems that can lead to sudden cardiac death due to defects in the cell-cell contacts.
A. Brodehl et al. (2012): Dual-color photoactivation localization microscopy of cardiomyopathy associated desmin mutants, Journal of Biological Chemistry, doi: 10.1074/jbc.M111.313841
Further informationPD Dr. Hendrik Milting, Erich and Hanna Klessmann - Institute for Cardiovascular Research and Development, Heart and Diabetes Center NRW, Ruhr-Universität Bochum, Georgstraße 11, Bad Oeynhausen, Tel. 05731/97-3510
Editor: Dr. Julia Weiler
Dr. Josef König | idw
Using fragment-based approaches to discover new antibiotics
21.06.2018 | SLAS (Society for Laboratory Automation and Screening)
Scientists learn more about how gene linked to autism affects brain
19.06.2018 | Cincinnati Children's Hospital 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
21.06.2018 | Earth Sciences
21.06.2018 | Life Sciences
21.06.2018 | Earth Sciences