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 to be 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 exampletension 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 otherhypothesized 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 ver
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Harvard Medical School