Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein shows talent for improvisation

18.04.2008
An unusual regulatory mechanism in the formation of contact sites between nerve cells

Radio and cable are not required for communication within and between living cells. Rather, signal transduction in cells is performed by a multitude of proteins.


A protein with two functions: Using a clever trick, the CASK kinase compensates - at least in part - for its low activity. One part of the protein actively recruits neurexin proteins and places them in close proximity to the kinase. Wahl / MPIbpc

In order to transfer and interpret these signals correctly, activities of these proteins have to be precisely synchronized. Their subtle regulation is controlled by a sophisticated system, in which so called protein kinases play a key role. An international team of scientists from Dallas (USA), Göttingen and Hamburg (Germany) have now discovered a kinase, which seems superior under difficult conditions. Whereas all known kinases function only in the presence of magnesium, the pseudokinase CASK has found a trick to do away with this trace element.

The protein seems to be directly involved in formation of contact sites - synapses - during early development of the nervous system. Pseudokinases like CASK have so far been considered inactive. At least some of them seem to have been labelled "not useful" without good reason in the past. (Cell, April 18, 2008)

Human beings must permanently adjust to new situations in their environment and react in an appropriate manner. Likewise, living cells receive a large number of signals which they need to transfer and to interpret. Often, cells are stimulated to grow or to divide, to start a developmental process or to initiate an immune response. To do so, numerous actors within cells - the proteins - have to perform in a precisely coordinated manner. A complex control system assures that these proteins work at the right time and at the right place. Central key players within this control system are specific proteins termed kinases. Up to 500 different kinases are present within a single cell; each of them regulates a particular subset of proteins. They activate or inhibit proteins, route them to a specific cellular location, or block their interaction with other cell components. To transmit their orders, kinases label corresponding proteins with a small phosphate group. The underlying reaction mechanism seems to be the same for all known kinases: With the help of magnesium, kinases bind an ATP-molecule and cleave off one phosphate group, which is subsequently transferred to the protein. A small number of kinases, however, lack the ability to bind magnesium normally required for the reaction. As so-called "pseudokinases" they have so far been largely disregarded in research. Wrongfully, as shown now by an international team of scientists of the University of Texas (Dallas, USA), the Max Planck Institute for Biophysical Chemistry (Göttingen, Germany) and the Deutsches Elektronen Synchrotron (Hamburg, Germany).

The researchers investigated a pseudokinase - the CASK kinase - which seems to be actively involved in early development of the nervous system. CASK interacts directly with the protein neurexin, which is required for correct formation of synapses between nerve cells. Mice lacking CASK kinase die shortly after birth. Humans without CASK develop mental disorders and blindness. "But CASK can not bind magnesium and without magnesium kinases usually do not work. For us, this just did not add up", says neurobiologist Konark Mukherjee, one of the project leaders of the University of Texas. Therefore, the scientists simulated the reaction in the test tube step by step. To their surprise the CASK kinase transferred phosphate groups completely without magnesium. When the scientists added magnesium to the test tube, the kinase was in fact inhibited. But is CASK also functional in a living cell? Indeed, the researchers could prove that the kinase performs in the same way in nerve cells of rats. In biological terms, the improvised reaction mechanism of CASK makes perfect sense. During synapse formation nerve cells contain little to no magnesium. Kinases, which depend on magnesium for function would simply not be functional", explains Mukherjee.

One protein - two functions
One exciting question for the scientists is now how a kinase can also do its job without magnesium. To better understand this novel reaction mechanism, neurobiologists and structural biologists worked closely together. Using X-ray crystallography, the scientists successfully solved the atomic structure of the CASK kinase. "In contrast to classic kinases CASK is virtually permanently active. But it reacts much slower in contrast to magnesium-dependent kinases", summarizes structural biologist Markus Wahl of the Max Planck Institute for Biophysical Chemistry the new insights into CASK function. The protein compensates its low activity - at least in part - by a clever trick: Besides the kinase domain, the protein contains another part, which actively recruits neurexin proteins and therefore facilitates their reaction with the kinase domain. "This way the pseudokinase can interact with the neurexin substrate for a longer time and label it with phosphate groups, although it acts slowly", explains Markus Wahl. The results of the researchers show that the reaction mechanism of kinases is much more multi-faceted than presumed earlier. Similarly, other pseudokinases, which lack typical features of kinases, could emerge as "specialists" which are functional under conditions where classical kinases would fail.
Contact:
Dr. Markus Wahl
Max Planck Institute for Biophysical Chemistry
Phone: +49 551 201-1046
Fax: +49 551 201-1197
E-Mail: mwahl@gwdg.de
Dr. Konark Mukherjee
University of Texas Southwestern Medical Center
Phone: +1 214-648-1903
Fax: +1 214-648-1801
E-Mail: konark.mukherjee@utsouthwestern.edu
Dr. Carmen Rotte
Public relations office, Max Planck Institute for Biophysical Chemistry
Phone: +49 551 201-1304
Fax: +49 551 201-1151
E-Mail: pr@mpibpc.mpg.de

Dr. Carmen Rotte | Max-Planck-Gesellschaft
Further information:
http://www.mpibpc.mpg.de/groups/wahl/
http://www.utsouthwestern.edu/utsw/cda/dept120915/files/144559.html

Further reports about: Biophysical CASK Kinase Magnesium Nerve Planck Pseudokinase Synapse phosphate

More articles from Life Sciences:

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

nachricht Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

NASA's Fermi catches gamma-ray flashes from tropical storms

25.04.2017 | Physics and Astronomy

Researchers invent process to make sustainable rubber, plastics

25.04.2017 | Materials Sciences

Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017

25.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>