Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Regulation of blood coagulation: Molecular switches guide blood forming cells

20.06.2017

Scientists from the University of Würzburg successfully elucidated new details about a circuit regulating platelet biogenesis. These important findings could contribute to a better understanding of the mechanism leading to bleeding disorders.

Platelets play a crucial role in hemostasis. At sites of vascular damage they attach to the subendothelial matrix, form a plug that seals the wound and contribute to tissue repair. Due to their short lifespan, new platelets need to be constantly generated.


Confocal microscope image of intact murine bone marrow. The mature megakaryocyte (green) attaches to blood vessel (red) and releases new platelets into the blood stream. Cell nuclei are shown in blue.

Photo: AG Nieswandt


Murine bone marrow under defective conditions. The lack of the Rho-GTPase ´RhoA´ in megakaryocytes (green) leads to their transmigration into blood vessel (red), impairing platelet biogenesis.

Photo: AG Nieswandt

To this end, giant precursor cells in the bone marrow, so-called megakaryocytes, undergo a complex maturation process and finally release platelets into the bloodstream. Defects in platelet biogenesis can result in dramatically decreased numbers or malfunctioning of circulating platelets, thus affecting hemostasis in patients. Unfortunately, the detailed mechanisms regulating megakaryocyte maturation and platelet biogenesis still remain elusive.

Modifications cause drastic consequences

Researchers from the Rudolf Virchow Center for Experimental Biomedicine and the University Hospital Würzburg now succeeded in identifying a decisive regulatory circuit in platelet biogenesis. The group of Prof. Bernhard Nieswandt was able to decipher vital regulating factors in megakaryocytes.

Small proteins, the Rho-GTPases, serve as molecular switches in the regulation of important cellular functions such as maturation, as well as orientation towards the blood vessels. Thus, the RHo-GTPases allow megakaryocytes to properly produce platelets.

´We could show that the complete absence or even a defect of these switches disrupts the orientation of the megakaryocyte, which then transmigrate through the blood vessel.´ says Prof. Nieswandt, director of the study. Indeed, under these conditions normal platelet biogenesis is abolished, leading to a drastic decrease in platelet count and bleeding complications in mice.

These astonishing findings built the basis for a new understanding of platelet generation in bone marrow and most likely also provide new insights into the development of other blood cells.

Therapeutical approach in bleeding disorders

The discovery of this Rho-GTPase-dependent regulatory circuit in platelet biogenesis encourages the scientists to gain new insights in bleeding disorders, such as the Bernard-Soulier Syndrome. Patients suffering from this disorder endure a severe reduction of the platelet count, which is accompanied by a life-long profound bleeding complication.

´Our results open the way for new therapeutic approaches to treat diseases which are connected to defective platelet biogenesis.´ hopes Prof. Nieswandt.
The scientists recently published their new findings together with other international researchers in the journal Nature Communications.

Publication:
Dütting, S. et al. (2017). A Cdc42/RhoA regulatory circuit downstream of glycoprotein Ib guides transendothelial platelet biogenesis. Nature Communications. 8, 15838 doi: 10.1038/ncomms15838.

Website:
http://www.rudolf-virchow-zentrum.de/home.html
http://www.virchow.uni-wuerzburg.de/lab_pages/nieswandt/

Contact:
Prof. Dr. Bernhard Nieswandt (Chair Experimental Biomedicine – Vascular Medicine, Rudolf-Virchow-Center)
Tel. +49 (0)9 31/ 31 - 80405, bernhard.nieswandt@virchow.uni-wuerzburg.de

Katja Aurbach (PhD student, Dept. Experimental Biomedicine - Vascular Medicine)
+49 (0)9 31/ 31 - 99813, aurbach_K1@ukw.de

Dr. Frank Sommerlandt (Public Science Center, Rudolf-Virchow-Center)
Tel. 0931 31 88449, frank.sommerlandt@uni-wuerzburg.de

Weitere Informationen:

http://www.rudolf-virchow-zentrum.de/home.html
http://www.virchow.uni-wuerzburg.de/lab_pages/nieswandt/

Dr. Frank Sommerlandt | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

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....

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

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>