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 A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>