Physiology and biophysics of outer hair cells: The cells of Dallos

Santos‐Sacchi, Joseph; Navaratnam, Dhasakumar

doi:10.1016/j.heares.2022.108525

Cited by 7 publications

(2 citation statements)

References 29 publications

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“…2B Although the anion-binding pocket is highly conserved and structurally similar across members of the SLC26 family and SLC26A5 families (Fig. 2C), mammalian prestin is the only member capable of displaying eletromotility 22 . Hence, the distinct stability responses we observe for dolphin prestin and mouse SLC26A9 point to a prestin's unique adaptation as a motor protein.…”

Section: Resultsmentioning

confidence: 99%

Folding of Prestin’s Anion-Binding Site and the Mechanism of Outer Hair Cell Electromotility

Lin

Haller

Bavi

et al. 2023

Preprint

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Prestin (SLC26A5) responds to transmembrane voltage fluctuations by changing its cross-sectional area, a process underlying the electromotility of outer hair cells and cochlear amplification. Prestin's voltage-dependent conformational rearrangements partially depend on the binding of Cl- to an electrostatic gap between the TM3 and TM10 helices. Using hydrogen-deuterium exchange mass spectrometry, we find that prestin displays an unstable anion-binding site, where folding of the amino termini of TM3 and TM10 is coupled to Cl- binding. This event shortens the TM3-TM10 electrostatic gap, thereby reducing prestin's cross-sectional area. These folding events upon anion-binding are absent in SLC26A9, an anion transporter closely related to prestin. We observe helix fraying of prestin's anion-binding site but cooperative unfolding of multiple peripheral helices, with implications to prestin's fast electromechanical rearrangements. These results highlight a novel role of the folding equilibrium of the anion-binding site in defining prestin's unique voltage-sensing mechanism and electromotility.

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Section: Resultsmentioning

confidence: 99%

Folding of Prestin’s Anion-Binding Site and the Mechanism of Outer Hair Cell Electromotility

Lin

Haller

Bavi

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Although the anion-binding pocket is highly conserved and structurally similar across members of the SLC26 family and SLC26A5 families (Figure 2C), mammalian prestin is the only member capable of displaying eletromotility (Santos-Sacchi and Navaratnam, 2022). Hence, the distinct stability responses we observe for dolphin prestin and mouse SLC26A9 point to a prestin's unique adaptation as a motor protein.…”

Section: Prestin's Anion-binding Site Is Less Stable Than Slc26a9smentioning

confidence: 92%

Folding of Prestin’s Anion-Binding Site and the Mechanism of Outer Hair Cell Electromotility

Lin

Haller

Bavi

et al. 2023

Preprint

View full text Add to dashboard Cite

Prestin responds to transmembrane voltage fluctuations by changing its cross-sectional area, a process underlying the electromotility of outer hair cells and cochlear amplification. Prestin belongs to the SLC26 family of anion transporters yet is the only member capable of displaying electromotility. Prestin’s voltage-dependent conformational changes are driven by the putative displacement of residue R399 and a set of sparse charged residues within the transmembrane domain, following the binding of a Cl- anion at a conserved binding site formed by amino termini of the TM3 and TM10 helices. However, a major conundrum arises as to how an anion that binds in proximity to a positive charge (R399), can promote the voltage sensitivity of prestin. Using hydrogen-deuterium exchange mass spectrometry, we find that prestin displays an unstable anion-binding site, where folding of the amino termini of TM3 and TM10 is coupled to Cl- binding. This event shortens the TM3-TM10 electrostatic gap, thereby connecting the two helices such that TM3-anion-TM10 is pushed upwards by forces from the electric field, resulting in reduced cross-sectional area. These folding events upon anion-binding are absent in SLC26A9, a non-electromotile transporter closely related to prestin. We also observe helix fraying at prestin’s anion-binding site but cooperative unfolding of multiple lipid-facing helices, features that may promote prestin’s fast electromechanical rearrangements. These results highlight a novel role of the folding equilibrium of the anion-binding site, and helps define prestin’s unique voltage-sensing mechanism and electromotility.

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Non-linear electro-rheological model of a membrane immersed in Tanner-Power law fluids applied to outer hair cells: Shear-thinning mechanisms

Ramírez-Torres,

Herrera-Valencia,

Sánchez-Villavicencio

et al. 2024

Physics of Fluids

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Flexoelectric actuation employs an applied electric field to induce membrane curvature, which is the mechanism utilized by the outer hair cells (OHC) present in the inner ear. The model developed for this study, representing the OHC, integrates two key components: (i) an approximation of the flexoelectric membrane shape equation for circular membranes attached to the inner surface of a circular capillary, and (ii) the coupled capillary flow of contacting liquid viscoelastic phases characterized by the Tanner-Power law rheological equation of state. A second-order non-linear differential equation for average curvature has been derived, and a robust numerical method has been programmed. This model simplifies to a linear model used previously. The main challenge involves identifying and describing the enhancement in curvature change rate. It was observed that low symmetry, low viscosity, and soft membrane and shear-thickening behavior of the phases enhance the curvature change rate. Additionally, there exists a critical electric field frequency value that maximizes the curvature change rate (resonance effect). The current theory, model, and computational simulations add to the ongoing development comprehension of how biological membrane shape actuation through electromechanical couplings.

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Physiology and biophysics of outer hair cells: The cells of Dallos

Cited by 7 publications

References 29 publications

Folding of Prestin’s Anion-Binding Site and the Mechanism of Outer Hair Cell Electromotility

Folding of Prestin’s Anion-Binding Site and the Mechanism of Outer Hair Cell Electromotility

Folding of Prestin’s Anion-Binding Site and the Mechanism of Outer Hair Cell Electromotility

Non-linear electro-rheological model of a membrane immersed in Tanner-Power law fluids applied to outer hair cells: Shear-thinning mechanisms

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