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Structure of inner-ear protein is key to both hearing and inherited deafness
Date:4/16/2010

(Boston, Mass., April 14, 2010) Rising from the top surface of each of the specialized receptor cells in our inner ears is a bundle of sensory cilia that responds to the movement of sound. As sensitive as they are fragile, these cilia can move to wisps of sound no larger than a moleculebut can shear at sounds that are larger than life.

Cilia function mechanically, fluttering back and forth in response to sound vibrations. The tug of the cilia creates tension in fine "tip links" that tether each cilium to its neighbor, causing them to pull open channels that allow ions to flow into the receptor cells. This ion movement into the receptor cells, called hair cells for their microscopic bundles of cilia, generates the electrical signals that go to the brain to be translated into the sound of, say, footsteps, or a sonata, or a helicopter landing.

The ciliatip link apparatus in the hair cell is a clever arrangement of spring-like and string-like protein molecules, yet their atomic structures and mechanical properties are not well known.

Now new work from the laboratories of David Corey, professor of neurobiology at Harvard Medical School and Howard Hughes Medical Institute investigator, and Rachelle Gaudet, associate professor of molecular and cellular biology at Harvard University's Faculty of Arts and Sciences, has discovered how the structure of a vital region of cadherin-23, one of two proteins that join to form each tip link, relates to the hearing process. Researchers found cadherin-23 to be stronger and stiffer than previously thought, a characteristic produced by calcium ions that bind within folds of the protein and tie the folds together. Furthermore, they found that many mutations to cadherin-23 cause inherited deafness by weakening the ability of calcium to hold the protein together.

"Our findings help explain a whole class of inherited deafness," says Corey. "Many, many different mutations that cause inherited
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Contact: David Cameron
david_cameron@hms.harvard.edu
716-432-0441
Harvard Medical School
Source:Eurekalert

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