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 Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)

nachricht CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New Study Will Help Find the Best Locations for Thermal Power Stations in Iceland

19.01.2017 | Earth Sciences

Not of Divided Mind

19.01.2017 | Life Sciences

Molecule flash mob

19.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>