Structural correlates of prestin activity

prestin 活性的结构相关性

基本信息

批准号：
10862035
负责人：
DHASAKUMAR S NAVARATNAM
金额：
$ 71.18万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10862035
关键词：
Actins Affect Anions Area Auditory Behavior Belief Biochemical Biological Cavia Cells Charge Chemicals Chlorides Cochlea Complex Contracts Coupling Cytoskeletal Proteins Cytoskeleton Data Dependence Disparity Electric Capacitance Electron Microscopy Electrophysiology (science)Environment Family Family member Freeze Substitution Freezing Frequencies Funding Genetic Goals Hearing Kinetics Knock-out Knockout Mice Lateral Link Lipids Location Mammals Mass Spectrum Analysis Measurement Measures Mechanics Membrane Metabolic Methods Molecular Morphology Motor Movement Mus Nature Outer Hair Cells Pathology Play Predisposition Process Property Proteins Proteomics Role Spectrin Structure Styrenes Testing Uncertainty Viscosity Work combat experimental study lipidomics maleic acid mechanical load member mutant nanodisk particle preservation pressure rat Pres protein response sensor single molecule superresolution microscopy tomography voltage

项目摘要

Twenty years after the identification of prestin, an anion transporter (SLC26) family member, as the lateral membrane motor protein of the outer hair cell (OHC), we are faced with the possibility of more fully understanding how this single molecule can influence the mammal’s exquisite sense of hearing. We propose to target a focused set of aims, including 1) determining the influence of mechanical load in governing prestin’s frequency dependence; simultaneous measures of sensor charge movement (complex NLC), electromotility are planned, 2) determining the effect of several cytoskeletal proteins on electromotility and charge movement and 3) ascertaining how the lipid and proteomic environment in the lateral wall changes along the tonotopic axis and its effects on sensor charge movement. In order to reach these goals, we will employ a host of genetic, electrophysiological, molecular biological and biochemical methods. We believe that the information that we obtain through these studies will aid in understanding how the OHC enables us to hear so well and in turn how we might combat pathologies of the OHC that afflict millions.

阴离子转运蛋白 (SLC26) 家族 prestin 被发现二十年后成员，作为外毛细胞（OHC）的侧膜运动蛋白，我们是面临着更全面地理解这个单一分子如何能够发挥作用的可能性我们建议以一组为目标。目标，包括 1) 确定机械负载对控制 prestin 的影响频率依赖性；同时测量传感器电荷运动（复杂 NLC），计划电动性，2）确定几种细胞骨架的影响蛋白质对电动势和电荷运动的影响，3) 确定脂质和电荷运动如何侧壁蛋白质组环境沿音调轴的变化及其影响为了实现这些目标，我们将采用许多传感器电荷运动。我们相信遗传、电生理、分子生物学和生化方法。我们通过这些研究获得的信息将有助于理解如何 OHC 使我们能够很好地听到声音，进而了解我们如何对抗疾病 OHC 影响数百万人。