Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovering the Missing "LINC" to Deafness

29.01.2013
Mutation in a genetic protein prevents hearing, reports a TAU researcher

Because half of all instances of hearing loss are linked to genetic mutations, advanced gene research is an invaluable tool for uncovering causes of deafness — and one of the biggest hopes for the development of new therapies.


The different position of cell nuclei in unhealthy (red) cells relative to healthy (blue) cells leads to deafness.

Now Prof. Karen Avraham of the Sackler Faculty of Medicine at Tel Aviv University has discovered a significant mutation in a LINC family protein — part of the cells of the inner ear — that could lead to new treatments for hearing disorders.

Her team of researchers, including Dr. Henning Horn and Profs. Colin Stewart and Brian Burke of the Institute of Medical Biology at A*STAR in Singapore, discovered that the mutation causes chaos in a cell's anatomy. The cell nucleus, which contains our entire DNA, moves to the top of the cell rather than being anchored to the bottom, its normal place.
Though this has little impact on the functioning of most of the body's cells, it's devastating for the cells responsible for hearing, explains Prof. Avraham. "The position of the nucleus is important for receiving the electrical signals that determine proper hearing," she explains. "Without the ability to receive these signals correctly, the entire cascade of hearing fails."

This discovery, recently reported in the Journal of Clinical Investigation, may be a starting point for the development of new therapies. In the meantime, the research could lead towards work on a drug that is able to mimic the mutated protein's anchoring function, and restore hearing in some cases, she suggests.

From human to lab to mouse

Prof. Avraham originally uncovered the genetic mutation while attempting to explain the cause of deafness in two families of Iraqi Jewish descent. For generations, members of these families had been suffering from hearing loss, but the medical cause remained a mystery. Using deep genetic sequencing, a technology used to sequence the entire human genome, she discovered that the hearing impaired members of both families had a mutated version of the protein Nesprin4, a part of the LINC group of proteins that links the cell's nucleus to the inner wall of the cell.

In the lab, Prof. Avraham recreated this phenomenon by engineering the mutation in single cells. With the mutation in place, Nesprin4 was not found in the area around the cell nucleus, as in healthy cells, but was spread throughout the entire cell. Investigating further, she studied lab mice that were engineered to be completely devoid of the protein.

Created in Singapore, the mice were originally engineered to study the biology of LINC proteins. The fact that they were deaf came as a complete surprise to researchers. Without this protein serving as an anchor, the cell nucleus is not located in the correct position within inner ear cells, but seems to float throughout. This causes the cells' other components to reorient as well, ultimately harming the polarity of the cells and hindering electrical signals. It's a mutation that took a heavy toll on the cells' ability to transfer sound signals, explains Prof. Avraham, rendering the mice deaf.

Given the similarity between mouse and human inner ear cells, researchers predict that the same phenomenon is occurring in human patients with a mutation in the Nesprin4 gene.

Looking for a wider impact

Prof. Avraham says that she and her collaborators are the first to reveal this mutation as a cause of deafness. "Now that we have reported it, scientists around the world can test for mutations in this gene," she notes. The mutation could indeed be a more common genetic cause of deafness in a number of populations. And because Nesprin4 belongs to a family of proteins that have been linked to other diseases, such as muscular coordination and degeneration disorders, this could prove a ripe area for further research.

At TAU, the research was supported by the National Institutes of Health — NIDCD and Israeli Center of Research Excellence, I-CORE.

G. Hunka | EurekAlert!
Further information:
http://www.aftau.org

More articles from Health and Medicine:

nachricht Finnish research group discovers a new immune system regulator
23.02.2018 | University of Turku

nachricht Minimising risks of transplants
22.02.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>