Researchers Discover Hearing Protein

Harvard researchers have identified the most important protein involved in hearing, which may be the first step toward eventual gene therapy for deafness.

Harvard Medical School (HMS) scientists will publish the study in Nature magazine in November, and announced their discovery on the magazine’s website Wednesday.

The protein, called TRPA1, provides the critical link between sound, which enters the ear as a wave, and electrical signals, which the brain interprets.

“It’s a tremendous discovery,” said HMS Professor M. Charles Lieberman, who directs a laboratory at the Massachusetts Eye and Ear Infirmary. “People have been wondering about this for years!”

TRPA1 belongs to a general family of proteins which are responsible for sensory abilities in various organisms, said HMS Professor David P. Corey, who led the study.

Although researchers say this finding holds no immediate clinical implications, the discovery of TRPA1 has laid down key information for future developments in therapy.

“We don’t know if a mutation could be found for [this] gene that causes deafness,” said neurologist Professor David Clapham, who studies TRP channels in nervous systems. “Distantly, the potential for curing deafness would be there.”

This research could augment the stem-cell based therapies being investigated currently, said postdoctoral research fellow Kelvin Kwan, who worked on the project.

In addition to hearing, the TRPA1 protein may also be responsible for distinguishing pitch, said Corey, who studies neurobiology and is also a Howard Hughes Medical Institute (HHMI) investigator.

Different groups of hair cells in the ear vibrate in response to different tones, and they also “push back” at the sounds, Corey said.

This response amplifies the signal that TRPA1 receives and helps the brain separate closely related pitches.

The protein will also help scientists identify the still unknown components of hearing.

“We now know the identity of this apparatus—now it’s like trying to figure out the watch from the gears,” Corey said. “We have to figure out all the other proteins involved, and how these proteins interact with one another to make [the whole structure] work.”

TRPA1 is located on the 100 to 150 protrusions called cilia on hair cells in the ear, which are “absolutely critical” for sound-hearing ability, Corey said.

“It’s fair to say that hair cells are among the most vulnerable elements in the inner ear,” said Lieberman. “Both congenital and acquired deafness is due in large part to hair cell loss.”

When sound waves travel into the ear, they first contact the eardrum and cause it to vibrate, Corey said.

The eardrum in turn causes three tiny bones inside the ear to vibrate. The last of these bones taps against a snail-shaped, fluid-filled structure called the cochlea, which houses the hair cells that produce the TRPA1 protein.

Vibrations passed onto the cochlea change the pressure of the fluid inside, and the cilia generate mechanical force by moving back and forth.

Structures attached to the cilia control the opening and closing of the TRPA1 protein. The opening of the TRPA1 protein causes a difference in electrical potential energy which spurs the hair cell to release neurotransmitters. These are picked up by nerve fibers and translated into electrical signals—the language that the brain understands.

—Staff writer Risheng Xu can be reached at xu4@fas.harvard.edu.