Free Online Database Of Diseases, Illnesses & Ailments


Hearing And Balance Rely On "Firm Handshake" Between Two Inner Ear Proteins

Harvard researchers in the US have for the first time described how a chemical bond resembling a "firm handshake" between two proteins in the inner ear is critical for hearing and balance. They hope the finding will lead to new research in noise-induced hearing loss and certain genetic diseases.

The team, led by Harvard Medical School (HMS) professor of neurobiology David Corey, and Rachelle Gaudet, professor of molecular and cellular biology at Harvard University's Faculty of Arts and Sciences, writes about the study in the 7 November online issue of Nature. Tip Links The inner ear contains hair cells that convert mechanical stimuli like head movements and sounds into neural signals for balance and hearing. The Harvard team has uncovered the characteristics of a critical and vulnerable area of the hair cells, a part known as the "tip link". Tip links are made of thin protein filaments or strings that physically connect the "cilia" or hairs on the hair cells.

When the head moves or sound vibrations enter the ear, they cause the cilia to move. This creates tension in the tip links, which begins a process that eventually sends nerve impulses to the brain.

Corey, Gaudet and colleagues sucessfully mapped the 3-D atomic structure of the tip links, and calculated the force that would be required to pull them apart.

"Tip links are absolutely vital to hair cells, and hair cells are absolutely vital for hearing and balance," Corey explains in a statement.

"We now have this new understanding of how noise can break a tip link and potentially cause a hearing problem," he adds. Firm Handshake Between Cadherins Tip links comprise two types of protein known as cadherins which join in the middle to make one long string.

Mutations in these cadherins often lead to balance disorders and congenital deafness. From recent studies looking at these proteins, scientists have proposed where they join to each other is likely to be the first area to rupture under stress.

So the team decided to investigate, and gave first author Marcos Sotomayor, a postdoctoral researcher in the Corey's lab, the job of testing the idea.

His first step was to synthesize, purify and crystallize a large quantity of the proteins bound to each other.

The team then took powerful X-rays of the highly ordered crystallized proteins using a 3000-foot long electron accelerator at Argonne National Laboratory.

By analyzing the diffraction pattern the X-rays made after passing through the crystal, together with biochemical data, Sotomayor was able to create a complete 3-D map of the chemical structure of the bond between the two proteins, with detail right down to the position of each atom.

This showed that the proteins grip each other like a handshake where the hands grab each other's wrists. Bond Interface Not Seen Before The team also discovered that the molecular handshake was not governed by calcium, as other scientists from previous studies had proposed, but by an extended and involved interface never seen before in bonds between cadherins.

Using supercomputers and the 3-D structure, the team simulated the dynamics of the proteins under different conditions, such as applying different forces that might pull the handshake apart.

Their calculations show it takes only half as much force to break the bond as it does to unfold the proteins themselves, which confirms that the bond is indeed the weakest part of the tip link.

They propose that while the tip link is strong enough to bear normal sound, it will be the first area of the hair cell to break under loud noises.

In another part of the study, the researchers discovered that certain mutations of the cadherin proteins, ones known to produce deafness, can weaken the bond, so it yields even to quieter noises.

The team is now looking to discover more things about the tip link structure, such as where the proteins join up with tension-activated ion channels at the tips of the cilia.

Funds from the National Institutes of Health, the National Science Foundation, and the Howard Hughes Medical Institute helped finance the study.

Most Viewed Pages

Recent Searches

Our Visitors Ask About

Medical News