hearnet.comare you at risk?featuresshop HEAReventspartners
hearnet.comabout HEARhelp uslinks

Current Features




Video PSA's



Active Physics for Schools

"Can't HEAR You Knocking" Video

chat us up join our email list

Defect in protein can impede hearing, Scripps research says
By Bruce Lieberman

April 19, 2004

The Scripps Research Institute

Tiny hairs arranged in bundles called stereocilia inside the ear's cochlea convert sound waves into electrical signals for the brain to interpret. San Diego scientists found that the cadherin 23 gene creates tiny links, which tie the hairs together and make hearing possible.

Scientists in La Jolla have identified the critical role a single gene plays in the ability to hear: the point at which sound waves in the inner ear are transformed into electrical signals to the brain.

The gene, cadherin 23, had already been pinpointed as one of about 100 genes involved in hearing. But exactly where in the inner ear it played a role, and how, was unknown.

Mutations in the gene have been implicated in deafness, including the devastating disease Usher syndrome, which causes both deafness and blindness.

"We know a lot about our sense of vision and smell and taste, but we have (had) no clue about the molecules which help us convert mechanical energy into electrical signals," said Ulrich Mueller, a scientist at The Scripps Research Institute in La Jolla whose study will appear in the journal Nature in coming weeks. The paper was released online this month.

Cadherin 23 "is now the first molecule," Mueller said in an interview.

While this latest finding is important, scientists cautioned that it is only one step toward understanding the complex genetic architecture that supports hearing. Whether it will someday lead to new treatments for deafness and diseases is uncertain. The gene, the researchers found, encodes a protein in the cochlea, the snail-like organ of the inner ear that marks the last passage of sound waves from the outside world before they are converted into electrical signals that the brain can then interpret.

Inside the cochlea are bundles of tiny hairs that are pushed against a membrane as sound waves traveling through a fluid-filled chamber underneath them exert pressure.

The hairs, called stereocilium, are arranged in bundles called stereocilia. The tip of each hair is bound to the one next to it by a tiny link, somewhat like a string tying two branches of a tree together.

The cadherin 23 gene, the researchers found, encodes a protein that makes these strings. Without them, hearing is impossible.

As the entire bundle of hairs bends to the pressure of sound waves, the strings pull at the hairs they are attached to opening a kind of door on the surface of each hair.

The door, called an ion channel, allows calcium and potassium ions floating in fluid inside the cochlea to flow into each hair and down toward vesicles leading to the brain.

The flow of ions from the cochlea and into the brain marks this transformation of sound waves into electrical signals a process called mechanotransduction.

"Something has to open this door, and this molecule that we're working on, cadherin 23 is a component of this machinery which helps open it," Mueller said.

His research team identified the role of cadherin 23 by scanning all known proteins in the human and mouse genomes to see which one fit the profile of proteins of the type that had already been associated with stereocilia.

They zeroed in on two families of genes: cadherins and integrins. They narrowed the field down to cadherin 23 based on its size and its known association with deafness and Usher syndrome.

Their next step was to see if laboratory animals genetically engineered without the cadherin 23 gene would also not have the links. Experiments with zebra fish, with researchers at the Oregon Hearing Research Center and Vollum Institute at Oregon Health & Science University, showed that very result.

While the cadherin 23 protein works to open the ion channels, another one called myosin 1c appears to play a role in closing them. Mueller said he hopes to build an even more complete picture.

"This (finding) gives us the opportunity to find other molecules that are associated with this, which plays into this very fundamental process," he said.

Konrad Noben-Trauth, a researcher at the National Institute on Deafness and Other Communication Disorders, at the National Institutes of Health, first identified the cadherin 23 gene in 2001, and suspected that it was important for stereocilia. Exactly how it worked was unknown.

The Scripps study "is one step forward in understanding the structure of the bundle and of mechanotransduction, the first step in the hearing process," Noben-Trauth said.

"There are still some questions open on this study, and I would argue that this finding needs further proof."

More work will be needed to show that the cadherin 23 gene actually holds the instructions for the links, he said. A separate experiment with mice, meanwhile, will be needed to show that mammals without the gene also never grow the links.

Mueller called the work an example of how the study of a deafness can help scientists better understand basic physiology.

"Disease has really helped us to define a component of a very fundamental biological process, and that helps us to gain an understanding of the disease," he said.

Bruce Lieberman: (619) 293-2836; bruce.lieberman@uniontrib.com


are you at risk? | features | shop H.E.A.R. | events | partners

about H.E.A.R. | help us | links | home

copyright 1995-2013 - all rights reserved - full trademark notice

search | disclaimer | photo credits |contact us