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SLC26a5(Prestin)在运输和膜插入过程中电压诱导的操作点偏移的成熟过程

Maturation of Voltage-induced Shifts in SLC26a5 (Prestin) Operating Point during Trafficking and Membrane Insertion.

作者信息

Zhai Feng, Song Lei, Bai Jun-Ping, Dai Chunfu, Navaratnam Dhasakumar, Santos-Sacchi Joseph

机构信息

Department of Surgery (Otolaryngology), Yale University School of Medicine, New Haven, CT, USA; Department of Otolaryngology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.

Department of Surgery (Otolaryngology), Yale University School of Medicine, New Haven, CT, USA; Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.

出版信息

Neuroscience. 2020 Apr 1;431:128-133. doi: 10.1016/j.neuroscience.2020.02.003. Epub 2020 Feb 13.

Abstract

Prestin (SLC26a5) is an integral membrane motor protein in outer hair cells (OHC) that underlies cochlear amplification. As a voltage-dependent protein, it relies on intrinsic sensor charge to respond to transmembrane voltage (receptor potentials), thereby effecting conformational changes. The protein's electromechanical actively is experimentally monitored as a bell-shaped nonlinear capacitance (NLC), whose magnitude peaks at a characteristic voltage, V. This voltage denotes the midpoint of prestin's charge-voltage (Q-V) Boltzmann distribution and region of maximum gain of OHC electromotility. It is an important factor in hearing capabilities for mammals. A variety of biophysical forces can influence the distribution of charge, gauged by shifts in V, including prior holding voltage or membrane potential. Here we report that the effectiveness of prior voltage augments during the delivery of prestin to the membranes in an inducible HEK cell line. The augmentation coincides with an increase in prestin density, maturing at a characteristic membrane areal density of 870 functional prestin units per square micrometer, and is likely indicative of prestin-prestin cooperative interactions.

摘要

Prestin(SLC26a5)是外毛细胞(OHC)中的一种整合膜运动蛋白,是耳蜗放大作用的基础。作为一种电压依赖性蛋白,它依靠内在的传感电荷来响应跨膜电压(感受器电位),从而引起构象变化。该蛋白的机电活性通过实验监测为钟形非线性电容(NLC),其幅度在特征电压V处达到峰值。这个电压表示prestin电荷-电压(Q-V)玻尔兹曼分布的中点以及OHC电运动性的最大增益区域。它是哺乳动物听力能力的一个重要因素。各种生物物理力可以通过V的变化来影响电荷分布,包括先前的保持电压或膜电位。在此我们报告,在可诱导的HEK细胞系中,将prestin递送至膜的过程中,先前电压的有效性会增强。这种增强与prestin密度的增加相吻合,在每平方微米870个功能性prestin单位的特征膜面密度下成熟,并且可能表明prestin-prestin协同相互作用。

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