Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mainz researchers identify novel factor involved in autophagy

12.02.2015

Insight may enable innovative approach for new concepts in the fight against neurodegenerative diseases

Neurodegenerative disorders such as Alzheimer's disease are typically characterized by protein deposits in the brain. These are comprised of defective, insoluble proteins which no longer fulfill their function and which cells are unable to break down.


The transparent nematode C. elegans, only 1 millimeter in length, has characteristics which include a short life cycle and a fixed number of cells. It serves as a model organism primarily for research in developmental biology, genetics, and neurobiology.

source: Dr. Andreas Kern, Mainz University Medical Center

The work group headed by Professor Christian Behl of the Institute of Pathobiochemistry of the University Medical Center of Johannes Gutenberg University Mainz has determined the RAB3GAP complex as a novel factor that influences the efficient degradation of proteins. The researchers were able to show that the complex plays an important role in autophagy, a physiological process that breaks down cellular proteins and organelles.

This insight opens up possible new options for the development of therapeutic and preventative approaches for neurodegenerative diseases. The work group has published the results of their research in the specialized journal Autophagy.

The team led by Professor Christian Behl and Dr. Andreas Kern showed that the RAB3GAP complex has a decisive influence on the process of protein degradation and represents an important element of the cellular autophagy network. Autophagy is a process in which cells digest their own components. These could be excessive or damaged organelles, such as mitochondria, invading pathogens, such as viruses or bacteria, or cytoplasmic macromolecules.

Autophagy serves on the one hand for the recycling of the building blocks of cells and the provision of energy, but is also activated specifically in stress situations. "The controlled protein degradation by autophagy is a core aspect of protein homoeostasis, which means the complex interplay between the formation, folding, and decomposition of proteins. We have extended our understanding of age-related disorders by identifying new factors involved in this process," said Professor Christian Behl.

The research group discovered that the RAB3GAP complex promotes the formation of autophagic vesicles. These are bubble-like structures with a lipid shell that envelop the substrates to be degraded. The autophagic vesicles then fuse with lysosomes, simple cell organelles, which contain digestive enzymes that break down the substrates into their component parts.

"The autophagic vesicles need lipid membranes to form, and the cell has to provide those. Our discovery suggests that RAB3GAP recruits the lipids required for the autophagic degradation of proteins," explained Dr. Andreas Kern of the Institute of Pathobiochemistry, who was responsible for the experiments.

It was previously known that the RAB3GAP complex is important for the regulation of the RAB GTPase RAB3, and that it influenced vesicle transport at the synapses, which are the contact points between nerve cells. The novel finding established that the complex indeed has a dual function, which is of particular relevance with regard to diseases of the nervous system.

The researchers made their discovery employing the nematode C. elegans, which serves as a simplified model, to study the human nervous system. In C. elegans, the biochemists were able to knock down approximately 2,500 individual genes using special molecular biological techniques and analyze the effects on protein aggregation. This allowed the identification of numerous genes that were associated with increased protein aggregation once they had been turned off. Subsequently, the precise functional characterization was completed using cultures of human cells.

The work group at the Institute of Pathobiochemistry was also able to demonstrate that the positive influence on autophagy by the RAB3GAP complex antagonizes that of a previously known negative autophagy regulator. "Our hypothesis is that it is the relative balance of the effects of these opposed molecules that determines the overall autophagic activity of cells. We believe that not only have we come closer to understand the autophagy process itself but also, and more importantly, that it may be possible to develop new approaches to the treatment and prevention of neurodegenerative diseases by means of targeted intervention in this process," stated Behl.

In addition to the Mainz-based team, biochemists from Goethe University Frankfurt am Main were also involved in the research project that stretched over several years. This received funding from a wide range of organizations, including the Alzheimer Forschung Initiative e.V., the German Research Foundation (DFG) – also within the framework of the Collaborative Research Center 1080: "Molecular and cellular mechanisms of neural homoeostasis" –, the European Research Council (ERC), and a number of foundations.

PUBLICATION:
Spang N., Feldmann A., Huesmann H., Bekbulat F., Schmitt V., Hiebel C., Koziollek-Drechsler I., Clement A.M., Moosmann B., Jung J., Behrends C., Dikic I., Kern A., Behl C., RAB3GAP1 and RAB3GAP2 modulate basal and rapamycin-induced autophagy. Autophagy 2014: 10(12):2297-309.
DOI:10.4161/15548627.2014.994359
http://www.tandfonline.com/doi/full/10.4161/15548627.2014.994359#tabModule

CONTACT:
Professor Dr. Christian Behl
Director of the Institute of Pathobiochemistry
University Medical Center of Johannes Gutenberg University Mainz
Duesbergweg 6, D 55099 Mainz – GERMANY
phone +49 6131 39-25890
fax +49 6131 39-25792
e-mail: cbehl@uni-mainz.de
http://www.unimedizin-mainz.de/pathobiochemie

Dr. Christine Ziegler
Institute of Pathobiochemistry
University Medical Center of Johannes Gutenberg University Mainz
Duesbergweg 6, D 55099 Mainz – GERMANY
Telefon +49 6131 39-24552
e-mail: christine.ziegler@uni-mainz.de
http://www.unimedizin-mainz.de/pathobiochemie

PRESS CONTACT:
Oliver Kreft, Press and Public Relations, Mainz University Medical Center
phone +49 6131 17-7424
fax +49 6131 17-3496
e-mail: pr@unimedizin-mainz.de
http://www.unimedizin-mainz.de/index.php?L=1

Weitere Informationen:

http://dx.doi.org/10.4161/15548627.2014.994359

Petra Giegerich | idw - Informationsdienst Wissenschaft

More articles from Health and Medicine:

nachricht Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences

nachricht What does congenital Zika syndrome look like?
24.03.2017 | 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: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>