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 Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

nachricht The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

IHP presents the fastest silicon-based transistor in the world

05.12.2016 | Power and Electrical Engineering

InLight study: insights into chemical processes using light

05.12.2016 | Materials Sciences

High-precision magnetic field sensing

05.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>