Evidence That Prestin Has at Least Two Voltage-dependent Steps

Peter Dallos,Kazuaki Homma

doi:10.1074/jbc.m110.185694

Peter Dallos, Kazuaki Homma

Open Access

https://doi.org/10.1074/jbc.m110.185694

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Abstract

Prestin is a voltage-dependent membrane-spanning motor protein that confers electromotility on mammalian cochlear outer hair cells, which is essential for normal hearing of mammals. Voltage-induced charge movement in the prestin molecule is converted into mechanical work; however, little is known about the molecular mechanism of this process. For understanding the electromechanical coupling mechanism of prestin, we simultaneously measured voltage-dependent charge movement and electromotility under conditions in which the magnitudes of both charge movement and electromotility are gradually manipulated by the prestin inhibitor, salicylate. We show that the observed relationships of the charge movement and the physical displacement (q-d relations) are well represented by a three-state Boltzmann model but not by a two-state model or its previously proposed variant. Here, we suggest a molecular mechanism of prestin with at least two voltage-dependent conformational transition steps having distinct electromechanical coupling efficiencies.

Highlights

The question of how prestin functions as a membranebased molecular motor has received a great deal of attention; even some fundamental issues are still obscure
We find that a Boltzmann model with at least two voltage-dependent steps is required for explaining prestin function
Because the observed charge movement should intimately relate to conformational change of the prestin molecule for generating motility, further detailed quantitative knowledge of the relation between charge movement and physical displacement is essential for better understanding the molecular mechanism of prestin

Summary

Introduction

The question of how prestin functions as a membranebased molecular motor has received a great deal of attention; even some fundamental issues are still obscure. The p values determined by Deming linear regression analyses (solid lines) followed by t tests for the y intercept (ϭ0) and the slope (ϭ1) were all greater than 0.05 for ␣1, ␣2, Vpk1, and Vpk2 comparisons, suggesting that the NLC and motility are coupled in terms of ␣1–␣2 and Vpk1–Vpk2.

Results

Conclusion