Scientists have finally unraveled the structure of a mysterious protein complex in the inner ear that enables hearing in humans.
To solve this decades-old mystery, researchers had to breed 60 million roundworms (Caenorhabditis elegans) that use a very similar protein complex to humans to sense touch.
Because humans only have a tiny amount of this protein in their inner ears, they turn to another source was the only way the team was able to accumulate enough protein for the study.
“We spent several years optimizing worm growth and protein isolation methods and had many ‘low point’ moments where we considered giving up,” says Co-first author Sarah Clark, a biochemist from Oregon Health and Science University (OHSU) in Portland.
Researchers have known for some time that the TMC1 (Transmembrane Channel-Like Protein 1) complex plays an important role in hearing, but the exact composition has remained elusive.
“This is the last sensory system in which this basic molecular machinery has remained unknown,” says senior author Eric Gouaux, senior biochemist at OHSU.
Thanks to this new research, published in Naturewe now know that this protein complex acts as a voltage-sensitive ion channel that opens and closes depending on the movement of the hairs in the inner ear.
Using electron microscopy, the researchers discovered that the protein complex “resembles an accordion,” with subunits arranged “like handles” on either side.
Sound waves traveling through the ear hit the eardrum (eardrum) and then the inner ear, where the ossicles wobble; three of the smallest bones in the body. The ossicles meet the snail-like cochlea, which in turn brushes microscopic finger-like hairs called stereocilia against membranes.
These stereocilia are embedded in cells that have the ion channels formed by the TMC1 complex, which open and close when hair moves and send electrical signals along the auditory nerve to the brain, which are interpreted as sound.
“The field of auditory neuroscience has been waiting for these results for decades, and now that they are here we are excited,” says OSHU ENT physician Peter Barr-Gillespie, a leading national hearing research expert, who was not involved in the study.
The discovery could one day help researchers develop treatments for hearing impairment.
Hearing loss and deafness affect more than 460 million people worldwide. By understanding the nature of hearing, researchers can continue to find different ways to support, treat, or prevent hearing loss in our community.
This paper was published in Nature.