Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Desminopathies: RUB researchers gain new insights into the mechanisms of heart disease

23.05.2012
Aggregating instead of stabilizing
Mutated and intact proteins of the cytoskeleton form abnormal aggregates

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.

Bibliographic record

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 information

PD 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

HMilting@hdz-nrw.de

Editor: Dr. Julia Weiler

Dr. Josef König | idw
Further information:
http://www.ruhr-uni-bochum.de

More articles from Health and Medicine:

nachricht Potential seen for tailoring treatment for acute myeloid leukemia
10.12.2018 | University of Washington Health Sciences/UW Medicine

nachricht UC San Diego researchers develop sensors to detect and measure cancer's ability to spread
06.12.2018 | University of California - San Diego

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

Im Focus: Substitute for rare earth metal oxides

New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals

Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.

Im Focus: A bit of a stretch... material that thickens as it's pulled

Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.

Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...

Im Focus: The force of the vacuum

Scientists from the Theory Department of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science (CFEL) in Hamburg have shown through theoretical calculations and computer simulations that the force between electrons and lattice distortions in an atomically thin two-dimensional superconductor can be controlled with virtual photons. This could aid the development of new superconductors for energy-saving devices and many other technical applications.

The vacuum is not empty. It may sound like magic to laypeople but it has occupied physicists since the birth of quantum mechanics.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

Expert Panel on the Future of HPC in Engineering

03.12.2018 | Event News

 
Latest News

Small but ver­sat­ile; key play­ers in the mar­ine ni­tro­gen cycle can util­ize cy­anate and urea

10.12.2018 | Life Sciences

New method gives microscope a boost in resolution

10.12.2018 | Physics and Astronomy

Carnegie Mellon researchers probe hydrogen bonds using new technique

10.12.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>