Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Controller in the Cell

09.06.2015

Frankfurt scientists discover new molecular mechanisms that eliminate intracellular damages. Mutations in this pathway trigger neurodegenerative diseases.

Quality control is important – this is not only applicable to industrial production but also true for all life processes. However, whereas an enterprise can start a large-scale recall in case of any doubt, defects in the quality control systems of cells are often fatal. This is seen in particular in neurodegenerative diseases such as Alzheimer's, Parkinson's, or amyotrophic lateral sclerosis (ALS), in which fundamental mechanisms of cellular quality control fail.


Ivan Dikic

GU

A Frankfurt research team led by Ivan Dikic, Professor for Biochemistry, now successfully decoded molecular details enabling a better understanding of two neurodegenerative diseases. Their work focuses on "autophagy" as a central element of cellular quality control.

Autophagy literally means "self-eating", and refers to a sophisticated system in which cellular waste is specifically detected, surrounded by membranes, and removed. Typical targets are harmful or superfluous proteins or cell organelles, even pathogens such as bacteria or viruses can be eliminated via this pathway.

Together with colleagues from Jena, Aachen, and The Netherlands, the team of Ivan Dikic has now identified a new autophagy receptor, the so-called FAM134B protein. In the online issue of the renowned journal Nature, the researchers report a new function of FAM134B in the constant renewal of the endoplasmic reticulum (ER), an important cell organelle. FAM134B ensures proper breakdown and disposal of dysfunctional ER.

"Too little FAM134B leads to an uncontrolled dilation and expansion of this organelle, which is harmful for the cell", explains Ivan Dikic. "The discovery of FAM134B as a new autophagy receptor is already a milestone. Even more exciting is the connection to a rare neuronal hereditary disease".

Collaborators from the Human Genetics Department at the University Hospital of Jena, PD Ingo Kurth and Professor Christian Hübner, already demonstrated in 2009 that mutations in FAM134B cause the death of sensory neurons in a disorder called hereditary sensory and autonomic neuropathy type II (HSAN II). The exact function of FAM134B, however, remained unknown until now.

HSAN II is a very rare hereditary disease in which both pain and temperature sensitivity and perspiration are impaired. For example, affected patients burn and hurt themselves easily, because they cannot feel heat and pain signals. Mutation of FAM134B in a mouse model leads to a similar syndrome "The mutated protein cannot function as a receptor. With these discoveries we have taken a big step to understanding the molecular causes of this neuropathy. At the same time, the importance of autophagy in cellular quality control is underlined", explains Dikic.

His laboratories at the Institute for Biochemistry II (IBC II) and at the Buchmann Institute for Molecular Life Sciences (BMLS) recently participated in another groundbreaking study of a neurodegenerative disease, ALS. Typically, ALS leads to death after three to four years due to the massive loss of motor neurons ALS (Amyotrophic lateral sclerosis ) is a devastating disease characterized by loss of motor neurons and neurodegeneration, usually leading to death within 3-4 years. Despite being classified as rare disease, public awareness is very high, fueled by celebrity patients like Stephen Hawking and culminating in last years’ Ice Bucket Challenge, the first charity campaign with global impact. Still, there is no treatment for ALS, despite intensive research in the field.

As reported in the title story of Nature Neuroscience’s May issue, an international team has now progressed significantly in understanding gene defects responsible for ALS. The scientists discovered that mutations in a specific enzyme, Tank-binding kinase (TBK1), occur more frequently in families with ALS. The Dikic lab was particularly involved in clarifying the function of TBK1 and was able to show that the mutations found in patients interrupt the interaction of TBK1 with the autophagy receptor optineurin. Optineurin is involved, for example, in the elimination of aggregated proteins and bacterial infection defense. Co-lead author Dr. Benjamin Richter comments: " For me as a medical doctor working in basic science this story represents the ideal case of explaining the pathophysiology of a disease by a collaborative effort across disciplines. ".

"The two studies show in an unparalleled way how general concepts can be developed from individual findings", emphasizes Ivan Dikic. When cellular quality control in neurons fails over a long time, the consequences for the overall organism are disastrous. "Autophagy has crystalized as a common central mechanism of cellular quality control in neurodegenerative disease", says Dikic.

Ivan Dikic (49) is leading his lab at the Goethe University in Frankfurt am Main since 2002; he is the director of Institute for Biochemistry II since 2009; and was the Founding Director of the Buchmann Institute for Molecular Life Sciences at the Riedberg Campus. Born in Croatia, he studied medicine in Zagreb, followed by a doctorate in natural sciences at the University of New York and the establishment of his first independent research group at the Ludwig Institute for Cancer Research in Uppsala (Sweden). In 2013, he received the Leibniz Prize of the German Research Foundation (DFG), the most prestigious German scientific prize. Furthermore, he has been honored with numerous other awards, including the Ernst Jung Prize for Medicine (2013), the William C. Rose Award of the American Society for Biochemistry and Molecular Biology (2013), and the German Cancer Prize (2010). He is a member of the German National Academy of Sciences and EMBO (European Molecular Biology Organisation) In 2010 he won an advanced investigator grant from the European Research Council (ERC), and he is the spokesperson for the LOEWE focus project Ubiquitin Networks, in the context of which parts of the now published work were done.


Publications:

A. Khaminets et al.: Regulation of endoplasmic reticulum turnover by selective autophagy. Nature, doi: 10.1038/nature14498, Advance Online Publication (AOP): http://www.nature.com/nature

A. Freischmidt et al.: Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia Natur Neuroscience, Nature Neuroscience 18, 631–636 (2015), doi:10.1038/nn.4000

Contact: Prof. Dr. Ivan Dikic, Goethe-Universität Frankfurt, Phone +49 (0)69 6301 5964, Email: dikic@biochem2.uni-frankfurt.de

Dr. Anke Sauter | idw - Informationsdienst Wissenschaft
Further information:
http://www.uni-frankfurt.de

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>