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 Small but ver­sat­ile; key play­ers in the mar­ine ni­tro­gen cycle can util­ize cy­anate and urea
10.12.2018 | Max-Planck-Institut für Marine Mikrobiologie

nachricht Carnegie Mellon researchers probe hydrogen bonds using new technique
10.12.2018 | Carnegie Mellon University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

Im Focus: Substitute for rare earth metal oxides

New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals

Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.

Im Focus: A bit of a stretch... material that thickens as it's pulled

Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.

Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...

Im Focus: The force of the vacuum

Scientists from the Theory Department of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science (CFEL) in Hamburg have shown through theoretical calculations and computer simulations that the force between electrons and lattice distortions in an atomically thin two-dimensional superconductor can be controlled with virtual photons. This could aid the development of new superconductors for energy-saving devices and many other technical applications.

The vacuum is not empty. It may sound like magic to laypeople but it has occupied physicists since the birth of quantum mechanics.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

Expert Panel on the Future of HPC in Engineering

03.12.2018 | Event News

 
Latest News

Small but ver­sat­ile; key play­ers in the mar­ine ni­tro­gen cycle can util­ize cy­anate and urea

10.12.2018 | Life Sciences

New method gives microscope a boost in resolution

10.12.2018 | Physics and Astronomy

Carnegie Mellon researchers probe hydrogen bonds using new technique

10.12.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>