20 December 2023
Our ability to detect different sounds intensities and pitches with great sensitivity is largely due to the inner ear's ability to decode sound waves and amplify individual frequencies. Since Prestin's discovery as the molecular membrane motor responsible for sound amplification in the inner ear in 2000, it has been the subject of great intrigue given prestin's membership in the Solute Carrier 26 (SLC26) protein family. In addition to evolving into a voltage-dependent membrane motor, mammalian Prestin lost the ability to transport solutes - leading to wide speculation as to its underlying molecular mechanisms. The other SLC26 proteins transport ions across the cell membrane using an elevator-transport mechanism, which involves a vertical movement of a mobile transport-domain against a static scaffold-domain. Mammalian Prestin's unique electrical and mechanical ability, known as electromotility, remained enigmatic so far.
Scientists from the Institute of Molecular and Cellular Physiology of Forschungszentrum Jülich (IBI-1) and Philipps-University Marburg now combined atomistic molecular-dynamics simulations on Jülich's supercomputers and advanced electrophysiological experiments, to provide a description of Prestin's electromotility. These results, now published in the renowned journal Nature Communications, revealed the molecular mechanisms of sound amplification by Prestin at atomic resolution. The researchers found that voltage fluctuations across so-called outer hair cells in the inner ear (caused by sound-induced vibrations) induce changes of Prestin from its compact to its expanded conformation, or vice versa. These conformational changes of Prestin trigger length changes of the hair cells and thus vibrations of the sound frequency to be amplified.
Social and scientific relevance
The mammalian ear has evolved exquisite sensitivity to different frequencies, important for human communication. These results provide important insights into sound processing and amplification in the inner ear and could help develop novel therapeutic approaches for deafness.
Original publication
Kuwabara, M.F., Haddad, B.G., Lenz-Schwab, D. et al. Elevator-like movements of prestin mediate outer hair cell electromotility. Nature Communications 14, 7145 (2023). https://doi.org/10.1038/s41467-023-42489-8
