Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Head in a Cage

11.06.2013
Fatty acid composition of diacylglycerols determines local signaling patterns

In the human body, lipids do not only serve as energy stores and structural elements, but they are also important signaling molecules. Disruptions of lipid signal transmission seem to be involved in diseases such as atherosclerosis and diabetes, as well as inflammation and pain.



In the journal Angewandte Chemie, researchers from Heidelberg have now reported on photoactivatable lipids that can be used to manipulate signaling processes in cells with both spatial and time resolution.

To communicate with each other and react to external stimuli, cells need signal-transmission mechanisms. The signal cascades involved are very complex and vary greatly from one cell type to the next. For example, one type of cascade involves the activation of phospholipase C, which then splits a membrane building block into inositol trisphosphate and the lipid diacylglycerol (DAG). These in turn serve as secondary messengers within the cell.

DAG anchors the enzyme protein kinase C (PKC) to the cell membrane and activates it. In addition, DAG can open certain calcium channels in the cell membrane, allowing calcium ions to flow into the cell. This stimulates further steps of the network and hence eventually trigger physiological responses, such as changes in gene expression.

Lipids as secondary messengers have received relatively little attention from researchers. Lipids consist of a head group and a “tail” made of a hydrocarbon chain that can vary greatly with regard to its length and the number, distribution, and arrangement of its double bonds. Previous investigations did not differentiate the effects of the different tails, only those of the heads.

Carsten Schultz and a team from the European Molecular Biology Laboratory (EMBL) in Heidelberg have now taken on this challenge. They synthesized DAG lipids with a variety of tails and locked their glycerol heads into “cages” – molecules attached so as to block and deactivate the head group.

The cages are designed with a built-in “break-away” point that breaks open upon irradiation with light to release the DAG. These types of photoactivatable molecules make it possible to deliver biologically active signal molecules at a specific time and place with subcellular resolution.

Through these experiments, the researchers were able to demonstrate that the activation of PKC is locally limited by DAG, whereas the elevation of internal calcium ion concentration through activation of calcium channels affects the entire cell. Surprisingly, these effects seem to be dependent on the fatty acid composition of the lipid. One of the DAG variants thus induced fewer, shorter, and weaker elevations of the calcium level, while another caused stronger, long-lasting calcium signals. A third had no significant influence on the intracellular calcium concentration.

“If this variability concerning the fatty acid composition should influence the control of cellular processes in most lipids, a completely new level of complexity has to be considered in cell biology”, says Schultz. “Furthermore, our results demonstrate that cells can respond to a given spatially confined signal both with a local and a global response pattern. Local signaling is particularly important in polarized and migrating cells, where different signals are needed at opposite ends of the cell.”

About the Author
Dr Carsten Schultz is an interdisciplinary team leader and Senior Scientist at the European Molecular Biology Laboratory (EMBL) in Heidelberg. His main research fields include the manipulation and visualization of intracellular signal transduction networks by using chemical biology, as well as the development of fluorescent detection systems, for example in applications concerning chronic lung disorders within the framework of the German Center for Lung Research (DZL) in Heidelberg.
Author: Carsten Schultz, European Molecular Biology Laboratory, Heidelberg (Germany), http://www.embl.de/research/units/cbb/schultz/members/index.php?s_personId=CP-60002438
Title: The Fatty Acid Composition of Diacylglycerols Determines Local Signaling Patterns

Angewandte Chemie International Edition, Permalink to the article: http://dx.doi.org/10.1002/anie.201301716

Carsten Schultz | Angewandte Chemie
Further information:
http://pressroom.angewandte.org

More articles from Life Sciences:

nachricht Colorectal cancer risk factors decrypted
13.07.2018 | Max-Planck-Institut für Stoffwechselforschung

nachricht Algae Have Land Genes
13.07.2018 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Research finds new molecular structures in boron-based nanoclusters

13.07.2018 | Materials Sciences

Algae Have Land Genes

13.07.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>