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Morphology control of the hair-cell bundle for frequency-selective auditory detection

Abstract : Hair cells of the inner ear operate as cellular microphones that convert sound-evoked vibrations into electrical signals. Each hair cell is endowed with a mechanosensitive hair bundle—a tuft of actin-filled and cylindrical stereocilia. Hearing starts when sound evokes deflections of the hair bundle. Deflections modulate tension in the tip links that interconnect stereocilia and convey force to mechanosensitive ion channels, resulting in ionic influx. The hair-bundle morphology is tightly coupled to hair-cell function as a frequency-selective detector: high-frequency hair cells have shorter hair bundles and morphological defects in the hair bundles are associated with deafness. Because hair cells do not regenerate in mammals, the mechanism that maintains the hair-bundle morphology throughout life is of great importance, yet has remained elusive. This PhD project aims at studying a feedback mechanism between mechanoelectrical transduction and hair-bundle morphology. With hair cells excised from a frog’s ear, we found that blocking the transduction channels or disrupting the tip links resulted in shortening (~15%) and widening (~17-60%) of the stereocilia. Hair bundles with blocked transduction channels showed a 2-fold increase in their stiffness, a change too large to be explained by shortening only. Electron microscopy revealed that spacing of the parallel actin filament in the core of the stereocilia does not change with blocked transduction channels or disrupted tip links. Widening thus probably resulted from an increase in the number of actin filaments constituting the stereociliary core. Inhibiting formins—proteins that promote actin polymerization—resulted in thinner stereocilia in control cells and nearly abolished stereocilia widening upon blockage of the MET channels. These observations suggest that the control of actin polymerization by the transduction channels is likely to be formin-dependent.
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Submitted on : Monday, January 10, 2022 - 9:55:08 AM
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Atitheb Chaiyasitdhi. Morphology control of the hair-cell bundle for frequency-selective auditory detection. Biochemistry, Molecular Biology. Université Paris sciences et lettres, 2021. English. ⟨NNT : 2021UPSLS072⟩. ⟨tel-03518699⟩



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