Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Firm Molecular Handshake Needed for Hearing, Balance

Published: Tuesday, November 13, 2012
Last Updated: Tuesday, November 13, 2012
Bookmark and Share
Researchers describe for the first time the structure of a bond formed by two proteins critical for hearing and balance.

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 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.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More Than 4,400+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Doubling Down on Dengue
HMS researchers have discovered two ways a compound blocks dengue virus.
Tuesday, April 26, 2016
Fighting Early Stage Alzheimer's
Mouse study suggests possibility of curbing early synapse loss in Alzheimer’s.
Monday, April 04, 2016
Breaking the Chain
Compound prevents multidrug-resistant fungi from pumping out drugs.
Tuesday, February 23, 2016
Breaking Point
Hotspots for DNA breaks cluster in specific genes in developing neurons.
Wednesday, February 17, 2016
The Spice of Life
Scientists discover important genetic source of human diversity.
Tuesday, February 09, 2016
Cytoskeleton Crew
Findings confirm sugar's role in helping cancers survive by changing cellular architecture.
Tuesday, February 09, 2016
The Power of Three
Overlooked portion of cell “death receptor” critical in some cancers, autoimmune diseases.
Tuesday, February 09, 2016
‘Lifespan Machine’ Probes Cause of Aging
Findings suggest that aging has no single mechanism.
Wednesday, February 03, 2016
Photo Finish
Nanoparticles pair photodynamic and molecular therapies against pancreatic cancer in mice.
Tuesday, January 26, 2016
High-fidelity CRISPR
Improved gene-editing tool has no detectable off-target mutations.
Thursday, January 07, 2016
Stem Cell Memory
Scientists find molecular key that prevents the conversion of adult cells into iPS cells.
Tuesday, January 05, 2016
Hit Parade
Researchers are generating a list of compounds that may lead to a trio of new therapeutics.
Tuesday, December 22, 2015
Stockpiling Proteins
New web-based tool allows researchers to measure protein dynamics in embryogenesis.
Wednesday, December 09, 2015
A Natural History of Neurons
Diverse mutations reveal lineage of brain cells.
Monday, October 05, 2015
The Final Word on STAP
Researchers fail to replicate STAP study; computational analysis reveals genomic inconsistency.
Monday, September 28, 2015
Scientific News
Releasing Cancer Cells for Better Analysis
A new device developed at the University of Michigan could provide a non-invasive way to monitor the progress of an advanced cancer treatment.
Releasing Cancer Cells for Better Analysis
A new device developed at the University of Michigan could provide a non-invasive way to monitor the progress of an advanced cancer treatment.
Apricot Kernels Pose Risk of Cyanide Poisoning
Eating more than three small raw apricot kernels, or less than half of one large kernel, in a serving can exceed safe levels. Toddlers consuming even one small apricot kernel risk being over the safe level.
Cell Transplant Treats Parkinson’s in Mice
A University of Wisconsin—Madison neuroscientist has inserted a genetic switch into nerve cells so a patient can alter their activity by taking designer drugs that would not affect any other cell.
Understanding Female HIV Transmission
Glowing virus maps points of entry through entire female reproductive tract for first time.
Genetic Markers Influence Addiction
Differences in vulnerability to cocaine addiction and relapse linked to both inherited traits and epigenetics, U-M researchers find.
Lab-on-a-Chip for Detecting Glucose
By integrating microfluidic chips with fiber optic biosensors, researchers in China are creating ultrasensitive lab-on-a-chip devices to detect glucose levels.
A lncRNA Regulates Repair of DNA Breaks in Breast Cancer Cells
Findings give "new insight" into biology of tough-to-treat breast cancer.
COPD Linked to Increased Bacterial Invasion
Persistent inflammation in COPD may result from a defect in the immune system that allows airway bacteria to invade deeper into the lung.
Detection of HPV in First-Void Urine
Similar sensitivity of HPV test on first void urine sample compared to cervical smear.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,400+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!