Navigation Links
Starting signal for antiviral defense

In human cells, DNA occurs only in the cell nucleus as the carrier of genetic information. In order to protect it, specialized proteins regularly scan the individual strands for defects, and repair them. One example of this is the protein Rad50, a DNA sensor that binds to DNA and detects defective sites. A team of scientists headed by Prof. Jrgen Ruland of the TUM together with colleagues from the LMU have now discovered another important task performed by Rad50.

There is normally no DNA in the cytoplasm surrounding the cell nucleus. However, if any does turn up there, it is frequently foreign DNA from a virus, for instance, that has infected the cell. Just like humans, some types of viruses use DNA to carry their genetic information. Thus the innate immune system has developed alarm mechanisms to detect foreign DNA in cytoplasm quickly and effectively, and activate the immune system by producing messenger substances.

However, it remains largely unclear just how this activation process occurs in the cytoplasm. In their study, lead author Dr. Susanne Roth and her colleagues have now shown that the DNA sensor Rad50 from the cell nucleus is also an important trigger for antiviral defense. "It is very surprising even for us that Rad50, which specializes in DNA in the cell nucleus, also detects foreign viral DNA and acts as a connecting link for the corresponding immune response", says Prof. Jrgen Ruland, explaining the significance of the findings.

One protein - two functions

In their experiments, the participating scientists infected immune cells with a virus that introduced its DNA into the cytoplasm. They were able to show that Rad50 bound to the viral DNA in the cytoplasm, even though it normally docks onto damaged DNA in the cell nucleus. A crucial factor was that Rad50 interacted with a specific signal protein (CARD9) of the immune system at the same time, forming a complex. The researchers succeeded in demonstrating this connection in cells for the first time.

The formation of the complex activated a signal transduction pathway in the cell which ended with production of the messenger substance interleukin 1β. This vital "global player" of the immune system is responsible for the onset of fever as a defense mechanism against pathogens, but also has a role in autoimmune diseases, such as rheumatoid arthritis.

In order to confirm their results, the researchers then used cells containing either no Rad50 or no CARD9, and again introduced DNA into their cytoplasm. Both cell types then produced far less interleukin 1β, as the Rad50-CARD9 complex could not be formed in order to activate the alarm system.

"Too much or too little of IL-1β can lead to a defective immune response or chronic disease, so its production must be strictly regulated by the body", explains Jrgen Ruland. "Now that we know Rad50 and CARD9 are important triggers for the alarm system and IL-1β production, we can gain a better understanding of many immune responses and develop strategies to influence them therapeutically."


Contact: Vera Siegler
Technische Universitaet Muenchen

Related biology news :

1. Starting a family does not encourage parents to eat healthier
2. ERC starting grant for Friederike Range
3. Unexpected discovery reveals a new mechanism for how the cerebellum extracts signal from noise
4. To drive infections, a hijacking virus mimics a cells signaling system
5. Tiny electrical sensors could signal faster MRSA diagnosis
6. Protein signal is crucial for accurate control of insect size
7. Deterring signals: Tobacco plants advertise their defensive readiness to attacking leafhoppers
8. Bacterium signals plant to open up and let friends in
9. Scientists tie DNA repair to key cell signaling network
10. Ion selectivity in neuronal signaling channels evolved twice in animals
11. Long-distance distress signal from periphery of injured nerve cells begins with locally made protein
Post Your Comments:
(Date:11/11/2015)...   MedNet Solutions , an innovative SaaS-based eClinical technology ... pleased to announce that it will be a Sponsor of ... to be held November 17-19 in Hamburg ... of iMedNet , MedNet,s easy-to-use, proven and ... has been able to deliver time and cost savings of ...
(Date:11/4/2015)... 2015 --> ... by Transparency Market Research "Home Security Solutions Market - Global ... - 2022", the global home security solutions market is expected to ... The market is estimated to expand at a CAGR ... 2022. Rising security needs among customers at homes, the ...
(Date:10/29/2015)... 2015  Rubicon Genomics, Inc., today announced an ... its DNA library preparation products, including the ThruPLEX ... Plasma-seq kit. ThruPLEX Plasma-seq has been optimized for ... libraries for liquid biopsies--the analysis of cell-free circulating ... in cancer and other conditions. Eurofins Scientific is ...
Breaking Biology News(10 mins):
(Date:12/1/2015)... Texas (PRWEB) , ... December ... ... , a leading relationship marketing company specializing in scientifically backed, age-defying products, ... January 2016 issue, which highlights the exponential success and unrivaled opportunities that ...
(Date:12/1/2015)... DIEGO , December 1, 2015 Dr. Harry Lander ... serving as Chief Science Officer and recruits ... Dr. Harry Lander , President of Regen, expands his role to ... and recruits five distinguished scientists to join ... Regen, expands his role to include serving ...
(Date:12/1/2015)... ) has ... Virology and Bacteriology Testing Market: Sales and ... Shares by Test, Innovative Technologies, Competitive Strategies, ... --> ) has announced the ... Bacteriology Testing Market: Sales and Volume Segment ...
(Date:11/30/2015)... MIAMI (PRWEB) , ... November 30, 2015 , ... ... opening of a new, Good Manufacturing Practice (GMP) 10000 in the Santiago Marriott. ... technologies available, and is operated by a world-class team of qualified medical researchers ...
Breaking Biology Technology: