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 4,500+ 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
The Rise of 3D Cell Culture and in vitro Model Systems for Drug Discovery and Toxicology
An overview of the current technology and the challenges and benefits over 2D cell culture models plus some of the latest advances relating to human health research.
World’s Largest Coral Gene Database
‘Genetic toolkit’ will help shed light on which species survive climate change.
A Boost for Regenerative Medicine
Growing tissues and organs in the lab for transplantation into patients could become easier after scientists discovered an effective way to produce three-dimensional networks of blood vessels, vital for tissue survival yet a current stumbling block in regenerative medicine.
Breast Cancer Drug Hope
A drug for breast cancer that is more effective than existing medicines may be a step closer thanks to new research.
Untangling Disease-Related Protein Misfolding
Work advances understanding of genetic forms of thrombosis, emphysema, cirrhosis of the liver, neurodegenerative diseases and inflammation, among others.
Early Genetic Changes in Premalignant Colorectal Tissue Identified
Findings point to drivers of early cancer development, targets for cancer prevention therapies.
Harnessing Nature’s Vast Array of Venoms for Drug Discovery
Scripps scientists have developed a method for rapidly identifying venoms.
Nanoparticles Target, Transform Fat Tissue
Nanoparticles designed to target white fat and convert it to calorie-burning brown fat slowed weight gain in obese mice without affecting food intake. This proof-of-concept work could lead to new therapies to treat obesity.
New Cancer Fighters Emerge From Lab
Rice University lab simplifies total synthesis of anti-cancer agent.
Scientists Find Evidence That Cancer Can Arise Changes
Researchers at Rockefeller University have found a mutation that affects the proteins that package DNA without changing the DNA itself can cause a rare form of cancer.
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
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!