Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scripps research scientists discover molecular defect involved in hearing loss

15.05.2009
Finding may lead to better understanding of how body responds to mechanical stimuli

Scientists from The Scripps Research Institute have elucidated the action of a protein, harmonin, which is involved in the mechanics of hearing. This finding sheds new light on the workings of mechanotransduction, the process by which cells convert mechanical stimuli into electrical activity.

Defects in mechanotransduction genes can cause devastating diseases, such as Usher's syndrome, which is characterized by deafness, gradual vision loss, and kidney disease, which can lead to kidney failure.

The research, led by Scripps Research Professor Ulrich Mueller, was published in the May 14, 2009 issue of the journal Neuron.

"We're constantly confronted with mechanical signals of many different kinds and we have sensors all over our bodies that respond to those signals," Mueller says. "For example, mechanosensors in the muscles control posture, while those in skin allow us to feel touch. Though many of our other senses, such as taste and smell, are well understood, mechanosensory perception is a world about which we know next to nothing."

By gaining a better appreciation of the molecular mechanics of hearing, scientists can learn a great deal about the workings of similar types of body processes and the defects in these processes that can cause disease.

Hearing: An Exquisite Molecular Dance

Sound starts as waves of mechanical vibrations that travel through the air to the ear by compressing air molecules. The waves first hit the outer ear, then travel down the ear canal into the middle ear before striking the eardrum. The vibrating eardrum moves a set of delicate bones that communicate with a fluid-filled spiral structure in the inner ear, the cochlea. Inside the cochlea are specialized "hair cells" lined with symmetric arrays of stereocilia – mechanosensing organelles that respond to fluid motion or fluid pressure changes. The movement of the fluid inside the cochlea causes the stereocilia, in turn, to move.

When sterocilia are deflected, molecular complexes called "tip links," which connect the tips of stereocilia, transmit physical force to the gated ion channels that are attached to them. The opening of these ion channels, which are monitored by sensory neurons, communicate the electrical signals to neurons in the brain, enabling hearing. In Usher syndrome and some other sensory neuronal diseases that cause deafness, the symmetry of the stereocilia – and the process of mechanotransduction – is disrupted, resulting in deafness.

"It has been known for some time that defects in the hair cells make people deaf, but no one knew why – it was thought that perhaps synapses in the hair cells somehow degenerate or the cells don't develop normally," Mueller says. "The idea that the hair cells' basic function as mechanotransducers were impaired as a result of molecular defects has never been shown before."

Building on Earlier Research

In part because stereocilia are extremely small, scarce, and difficult to handle, the molecules that make up the tip link remained elusive until 2007, when Mueller and his colleagues identified cadherin 23 and protocadherin 15 as the two proteins responsible for opening the ion channels. They also showed that cadherin 23 formed a complex with another protein, myosin 1c, which helped close the channel.

"Cadherin 23 and protocadherin 15 were two of the first known components of any mechanotransduction machinery of sensory cells in vertebrates," Mueller says. "Having these two components, we then went looking for others and found harmonin, which localizes to the tip link where cadherin 23 is also localized, and which we now know is required for mechanotransduction."

Having identified harmonin as yet another molecule involved in mechanotransduction, scientists may be able to move a little closer to addressing a basic science puzzle: How do biological systems build gating systems that act as mechanical devices, almost like switches? Similar switches are present in almost every cell in the body and are the gatekeepers that let ions flow in and out of a cell. Any given cell might have hundreds or thousands of channels. The right stimulus can throw a channel open, allowing ions to pass through; the surge of ions across the cell membrane generates tiny electrical currents that enable a multitude of bodily functions.

"Many different diseases are related to mechanical phenomena," Mueller says. "Understanding the components of this machinery may help shed light on many of them, leading ultimately to new treatments."

The first authors of the paper, "Harmonin (protein) mutations cause mechanotransduction defects in cochlear hair cells," are Nicolas Grillet, Wei Xiong, and Anna Reynolds of Scripps Research. Additional authors include Takashi Sato and Bechar Kachar of the National Institute of Deafness and other Communication Disorders, National Institutes of Health (NIH); Conception Lillo and David Williams of the University of California, Los Angeles, School of Medicine; Rachel Dumont and Peter Gillespie of the Oregon Health & Science University; and Piotr Kazmierczak, Edith Hintermann, Anna Sczaniecka, and Martin Schwander of Scripps Research.

The work was funded by the NIH, the Skaggs Institute for Chemical Biology, a Jules and Doris Stein RPB professorship, a C.J. Martin fellowship NHMRC (Australia), and a fellowship from the Bruce Ford and Anne Smith Brady Foundation.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California with a second campus located in Jupiter, Florida. Research at Scripps Florida focuses on basic biomedical science, drug discovery, and technology development.

Mika Ono | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>