Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A one way gate for tau proteins

27.10.2011
Scientists from Bonn have discovered a possible mechanism of Alzheimer disease

For a nerve cell to function properly, each protein must be in the right place.

The tau protein, for example, has to be located in the axons - the long projections of nerve cells. An early sign of a number of neurodegenerative diseases, in particular Alzheimer disease, is the redistribution of tau from the axons to the cell body.

Scientists at the German Center for Neurodegenerative Diseases (DZNE) and the research center caesar, lead by Prof. Eckhard Mandelkow, have now found an explanation for this mislocalization. They have discovered a new cellular mechanism that keeps tau protein in the axons in healthy cells and show how this process malfunctions in certain diseases. "The mechanism functions like a one-way gate at the axon junction, through which tau may enter the axon but which would prevent its return to the cell body" said Mandelkow. "In Alzheimer disease and other so-called tauopathies, tau is altered so that it can pass through the gate in both directions and thus becomes mislocalized." The work was published on October 18, 2011 online in the EMBO Journal.

"Tauopathies" is an umbrella term for a number of neurodegenerative diseases, of which Alzheimer disease is the most prominent representative. In normal cells, tau is enriched in the axons – cellular processes through which neuronal signals are passed on to downstream cells. In tauopathies, however, the protein is distributed throughout the cell body and its dendrites, the recipients of neural signals. This mislocalization of tau is a first and very crucial step in the pathology of the diseases. In previous work the teams of Eva and Eckhard Mandelkow have found evidence that the accumulation of tau in dendrites interferes with the neuronal contacts and thereby affects signal transmission between nerve cells. In the long term, this leads to the degeneration and loss of cells. The researchers thus wanted to investigate how tau is maintained in the axon in healthy cells and why this process is impaired in tauopathies.

To explore this issue in more detail, the scientists used a new technology that allows tracking the distribution of proteins within a cell. To this end, they coupled the tau protein with a photoactivated fluorescent dye and introduced it into neuronal cells. When a certain area of the cell is then stimulated briefly with a laser, the fluorescence properties of the tau protein change from green to red, so that its further spreading within the cell can be observed. The researchers showed that tau, once in the normal axon, is virtually trapped there. At the axon initial segment, where the axon branches off from the cell body, the scientists discovered a barrier that prevents tau protein from moving back from the axon into the cell body.

In healthy cells, tau binds to and stabilizes microtubules, components of the cytoskeleton, in the axons of the cells. In Alzheimer disease and other tauopathies, tau is covered with too many phosphate groups. This excessive phosphorylation causes removal of tau from the cytoskeleton and aggregation.

Could this process also contribute to the mislocalization of tau to the cell body? Could it be that the barrier at the initial axonal segment is only effective when tau is firmly bound to microtubules? Through further experiments the researchers were able to unambiguously answer these questions with "yes" - tau that is highly phosphorylated is able to leave the axon and accumulate in the cell body. "It has been recognized for a long time that tau protein is mislocalized in tauopathies. Moreover, the fact that tau bears too many phosphate groups in these diseases is common knowledge. Our studies now show that there is a connection between the two processes. Tau is sorted incorrectly because it is excessively phosphorylated, "said Mandelkow. Further studies are underway to evaluate the cause of this underlying hyperphosphorylation.

Original publication:
Xiaoyu Li, Yatender Kumar, Hans Zempel, Eva-Maria Mandelkow, Jacek Biernat and Eckhard Mandelkow. Novel diffusion barrier for axonal retention of Tau in neurons and its failure in neurodegeneration. The EMBO Journal, advanced online publication: 18.10.2011
Contact information:
Dr. Katrin Weigmann
German Center for Neurodegenerative Diseases (DZNE)
Press and Public Relations
Phone: +49 228 43302 /263
Mobile: +49 173 – 5471350
Email: katrin.weigmann@dzne.de

Katrin Weigmann | idw
Further information:
http://www.dzne.de

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>