Date
15
Sep 2025
Time
14:00:00
Institut Pasteur, Rue du Docteur Roux, Paris, France
Address
Building: François Jacob Room: Auditorium
Location
2025-09-15 14:00:00
2025-09-15 16:00:00
Europe/Paris
Lab seminar – Prestin Conformational Dynamics and the Molecular Basis of the Auditory Amplification
Mammals have evolved a highly sophisticated sense of hearing, with extraordinary sensitivity and high-frequency discrimination provided by a dynamic amplification mechanism in the outer hair cells (OHCs) in the organ of Corti. In the […]
Institut Pasteur, Rue du Docteur Roux, Paris, France
Pierre-Jean Corringer
pjcorrin@pasteur.fr
About
Mammals have evolved a highly sophisticated sense of hearing, with extraordinary sensitivity and high-frequency discrimination provided by a dynamic amplification mechanism in the outer hair cells (OHCs) in the organ of Corti. In the early 2000s the molecule responsible for OHC electromotility was identified as Prestin, a member of the SCL transporter superfamily highly expressed in OHCs. Prestin is capable of transducing changes in membrane potential into mechanical movement, and earlier work suggests that amplification arises from the concerted action of millions of Prestin motors (up to ~10,000 copies/µm2). Importantly, prestin dysfunction yields up to 50 dB of high frequency hearing loss.Yet the mechanism by which prestin converts sound-elicited receptor potentials into mechanical movement remains unclear and represents a major unsolved question in sensory physiology. The electromechanical process in OHCs that underlies cochlear amplification involves changes in the physical state of the cell membrane, including changes in membrane thickness. We determined multiple high-resolution structures of prestin in lipid nanodiscs of varying thicknesses using single particle cryo-electron microscopy. We have used a combination of cryoEM, electrophysiology, targeted mechanical perturbations and computational analyses to address three key questions related to prestin electromechanical transduction process: the origin of electromotility; the molecular basis of voltage sensing; and the nature of prestin force generation at the mesoscale. These structural insights offer a high-resolution understanding of how prestin transduces membrane perturbations into cochlear amplification.
Partners
Location
Building: François Jacob
Room: Auditorium
Address: Institut Pasteur, Rue du Docteur Roux, Paris, France