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:
Katrin Weigmann | idw
When fat cells change their colour
28.10.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau
Aquaculture: Clear Water Thanks to Cork
28.10.2016 | Technologie Lizenz-Büro (TLB) der Baden-Württembergischen Hochschulen GmbH
Physicists from the University of Würzburg have designed a light source that emits photon pairs. Two-photon sources are particularly well suited for tap-proof data encryption. The experiment's key ingredients: a semiconductor crystal and some sticky tape.
So-called monolayers are at the heart of the research activities. These "super materials" (as the prestigious science magazine "Nature" puts it) have been...
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
28.10.2016 | Power and Electrical Engineering
28.10.2016 | Physics and Astronomy
28.10.2016 | Life Sciences