Cytoskeletal stability in stereocilia maintenance

静纤毛维持中的细胞骨架稳定性

基本信息

批准号：
10649649
负责人：
BENJAMIN J PERRIN
金额：
$ 38.89万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-01 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10649649
关键词：
Actin-Binding Protein Actins Address Affect Aging Alleles Apical Architecture Auditory Binding Binding Proteins Biochemical Biological Assay Bundling CDH23 gene Cells Characteristics Cochlea Cytoskeletal Proteins Cytoskeleton Data Defect Development Dimensions Distal Epidermal Growth Factor Receptor Pathway Substrate 8 F-Actin Filament Genetic Grant Growth Hair Cells Hearing Human Knock-out Knockout Mice Labyrinth Length Maintenance Measures Membrane Microfilaments Modeling Monitor Mutation Myosin ATPase Noise Noise-Induced Hearing Loss Pattern Permeability Persons Polymers Population Presbycusis Proteins Regulation Research Rod Role Sensory Shapes Solubility Stereocilium Structure Surface Testing Thinness Time Width Work base cofilin congenital deafness deafness experimental study hearing impairment inhibitor malformation mechanotransduction mouse model novel overexpression polymerization predictive modeling progressive hearing loss repaired sound stem

项目摘要

PROJECT SUMMARY Hearing depends on stereocilia, which are protrusions on sensory cells in the inner ear that exist as membrane-enclosed bundles of actin filaments. If stereocilia are malformed during development or improperly maintained, then people have congenital deafness or progressive hearing loss. The composition of the stereocilia actin core is well-known and consists of a highly stable bundle of parallel actin filaments which form a stiff rod. The core dimensions dictate the length and width of stereocilia. The addition or loss of actin from the distal end of the core drives growth during development and shortening that occurs during some forms of progressive hearing loss. Our proposed experiments focus on elucidating how actin is regulated at the tips of developing stereocilia. Similar regulatory mechanisms may repair stereocilia during aging or following noise damage. Understanding these mechanisms is therefore expected to be essential for understanding many forms of hearing loss. This proposal builds on work done during the previous granting period, where we discovered differences in actin turnover at the tips of stereocilia in mechanotransducing rows. We now present evidence of a novel population of short actin filaments that exist at stereocilia tips but are not part of the actin core. Experiments in mouse models will document the key characteristics of these tip filaments, how they are regulated at the tips of mechanotransducing and non-mechanotransducing stereocilia, and how they contribute to stereocilia development and maintenance.

项目摘要听力取决于立体膜，这是对内耳感官细胞的突起，而存在肌动蛋白丝的膜封闭束。如果立体胶质在开发过程中畸形或不正确维持，人们会有先天性的耳聋或渐进的听力损失。的组成立体胶质肌动蛋白核心是众所周知的，由一块高度稳定的平行肌动蛋白丝组成，形成僵硬的杆。核心尺寸决定了立体尾膜的长度和宽度。从核心的远端驱动在某些形式的开发和缩短过程中的增长渐进的听力损失。我们提出的实验着重于阐明在发展立体胶质。类似的调节机制可能会在老化或随后的噪音期间修复立体胶质损害。因此，理解这些机制对于理解许多机制至关重要听力损失的形式。该提议建立在上一期授予期间所做的工作的基础上在机械转换行中，在立体胶质的尖端发现了肌动蛋白周转的差异。我们现在在场立体尾尖端存在的短肌动蛋白丝的新型人群的证据，但不是肌动蛋白的一部分核。鼠标模型中的实验将记录这些尖端细丝的关键特征，它们的状态在机械转换和非机械转换的立体胶质的尖端调节，以及它们如何贡献立体传播和维护。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The stable actin core of mechanosensory stereocilia features continuous turnover of actin cross-linkers.

机械感觉静纤毛的稳定肌动蛋白核心具有肌动蛋白交联剂的连续周转的特征。

DOI：
10.1091/mbc.e18-03-0196
发表时间：
2018
期刊：
Molecular biology of the cell
影响因子：
3.3
作者：
Roy,Pallabi;Perrin,BenjaminJ
通讯作者：
Perrin,BenjaminJ

Actin at stereocilia tips is regulated by mechanotransduction and ADF/cofilin.

DOI：
10.1016/j.cub.2020.12.006
发表时间：
2021-03-22
期刊：
Current biology : CB
影响因子：
0
作者：
McGrath J;Tung CY;Liao X;Belyantseva IA;Roy P;Chakraborty O;Li J;Berbari NF;Faaborg-Andersen CC;Barzik M;Bird JE;Zhao B;Balakrishnan L;Friedman TB;Perrin BJ
通讯作者：
Perrin BJ

Stereocilia morphogenesis and maintenance through regulation of actin stability.

DOI：
10.1016/j.semcdb.2016.08.017
发表时间：
2017-05
期刊：
Seminars in cell & developmental biology
影响因子：
7.3
作者：
McGrath J;Roy P;Perrin BJ
通讯作者：
Perrin BJ

PNPase knockout results in mtDNA loss and an altered metabolic gene expression program.

DOI：
10.1371/journal.pone.0200925
发表时间：
2018
期刊：
PloS one
影响因子：
3.7
作者：
Shimada E;Ahsan FM;Nili M;Huang D;Atamdede S;TeSlaa T;Case D;Yu X;Gregory BD;Perrin BJ;Koehler CM;Teitell MA
通讯作者：
Teitell MA