Featured Research

from universities, journals, and other organizations

Firm molecular handshake needed for hearing and balance

Date:
November 7, 2012
Source:
Harvard Medical School
Summary:
Researchers have mapped the precise 3-D atomic structure of a thin protein filament critical for cells in the inner ear and calculated the force necessary to pull it apart. These findings show the characteristics of the most vulnerable area of a structure called the tip link, and open avenues for research in fields related to noise-induced hearing loss and certain genetic diseases.

Researchers have mapped the precise 3-D atomic structure of a thin protein filament critical for cells in the inner ear and calculated the force necessary to pull it apart.

In a study to be published November 7 in the journal Nature, a group led by David Corey, HMS professor of neurobiology, and Rachelle Gaudet, professor of molecular and cellular biology in the Faculty of Arts and Sciences at Harvard University, revealed the characteristics of the most vulnerable area of a structure called the tip link. Their findings open avenues for research in fields related to noise-induced hearing loss and certain genetic diseases.

"Tip links are absolutely vital to hair cells, and hair cells are absolutely vital for hearing and balance," said Corey. "We now have this new understanding of how noise can break a tip link and potentially cause a hearing problem."

The sensations of hearing and balance rely on hair cells, a family of cells located in the inner ear. Crucial to their function are tip links, strings of protein that physically connect the cilia or "hairs" found on these cells. When the cilia move in response to sensory stimuli -- head movement or the vibration of sound, for example -- tension is applied to the tip links, which begins a process that ultimately sends nerve impulses to the brain.

Tip links are composed of two different types of proteins called cadherins, which connect in the middle to make one long string. Mutations in these proteins often result in congenital deafness and balance disorders. Scientists have only recently made strides toward understanding the nature of these cadherins, especially at their connection to each other -- hypothesized to be the first area to break under stress.

To test this, Marcos Sotomayor, first author on the paper and a postdoctoral researcher in the lab of David Corey, investigated the structure of that bond.

He first synthesized and purified a large amount of the very ends of the proteins, where they connect. After crystallizing the purified proteins bound to each other, the team took advantage of powerful X-rays generated by a 3000-foot long electron accelerator at Argonne National Laboratory.

When X-ray light passes through a highly ordered crystal, it creates a regular diffraction pattern that can be used to reveal the structure of the proteins forming the crystal.

Sotomayor analyzed the diffraction pattern generated at Argonne and coupled it with biochemical data. From this, he created a complete 3-D map of the structure of bonded region, down to the position of each individual atom.

The map revealed that the two different cadherins bonded like two hands gripping each other's wrists. This molecular handshake was not mediated by calcium ions, as had been hypothesized, but it showed an intimate and extended interface not seen before in cadherin-cadherin bonding.

With this precise 3-D structure, the team used supercomputers to simulate the dynamics of these proteins under a variety of conditions, including applying forces to pull the bond apart. They found that it takes only half as much force to break the connection as it does to unfold the cadherins themselves -- confirming that the bond is indeed the weakest region of the tip link. They suggest the tip link is strong enough to withstand normal sound, but the connection is likely the first to break under loud noises.

They also showed how certain mutations that produce deafness could weaken the bond, perhaps allowing it to come apart even with quiet sound.

The group plans to characterize tip-link structure further, moving on to other parts such as where the cadherins link to tension-activated ion channels at the tips of the hair cells' cilia.


Story Source:

The above story is based on materials provided by Harvard Medical School. Note: Materials may be edited for content and length.


Journal Reference:

  1. Marcos Sotomayor, Wilhelm A. Weihofen, Rachelle Gaudet, David P. Corey. Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction. Nature, 2012; DOI: 10.1038/nature11590

Cite This Page:

Harvard Medical School. "Firm molecular handshake needed for hearing and balance." ScienceDaily. ScienceDaily, 7 November 2012. <www.sciencedaily.com/releases/2012/11/121107132906.htm>.
Harvard Medical School. (2012, November 7). Firm molecular handshake needed for hearing and balance. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2012/11/121107132906.htm
Harvard Medical School. "Firm molecular handshake needed for hearing and balance." ScienceDaily. www.sciencedaily.com/releases/2012/11/121107132906.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Microneedle Patch Promises Painless Pricks

Microneedle Patch Promises Painless Pricks

Reuters - Innovations Video Online (Oct. 18, 2014) Researchers at The National University of Singapore have invented a new microneedle patch that could offer a faster and less painful delivery of drugs such as insulin and painkillers. Video provided by Reuters
Powered by NewsLook.com
Raw: Nurse Nina Pham Arrives in Maryland

Raw: Nurse Nina Pham Arrives in Maryland

AP (Oct. 17, 2014) The first nurse to be diagnosed with Ebola at a Dallas hospital walked down the stairs of an executive jet into an ambulance at an airport in Frederick, Maryland, on Thursday. Pham will be treated at the National Institutes of Health. (Oct. 16) Video provided by AP
Powered by NewsLook.com
Raw: Cruise Ship Returns to US Over Ebola Fears

Raw: Cruise Ship Returns to US Over Ebola Fears

AP (Oct. 17, 2014) A Caribbean cruise ship carrying a Dallas health care worker who is being monitored for signs of the Ebola virus is heading back to Texas, US, after being refused permission to dock in Cozumel, Mexico. (Oct. 17) Video provided by AP
Powered by NewsLook.com
Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

AFP (Oct. 17, 2014) All four suspected Ebola cases admitted to hospitals in Spain on Thursday have tested negative for the deadly virus in a first round of tests, the government said Friday. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins