Myosin 7a isoforms in functional diversity of cochlear hair cells

耳蜗毛细胞功能多样性中的肌球蛋白 7a 亚型

基本信息

  • 批准号:
    9925302
  • 负责人:
  • 金额:
    $ 16.15万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-07-01 至 2020-06-30
  • 项目状态:
    已结题

项目摘要

Abstract In the mammalian cochlea, inner hair cells (IHCs) operate as auditory receptors, while outer hair cells (OHCs) provide the cellular basis for cochlear amplification. It is well established that hair cell mechanotransduction (MET) properties, such as resting open probability, differ significantly between the two cochlear hair cell types. The molecular basis of these differences, and their significance for the respective functions of OHCs and IHCs, are not known. In preliminary studies, we discovered that two isoforms of Myosin VIIa (MYO7A) are expressed in the cochlea, generated by alternative start sites. Analysis of isoform-specific KO mice demonstrated that the longer MYO7A isoform is preferentially expressed in IHCs, while the shorter isoform, which lacks an 11-amino acid N-terminal extension, is predominantly expressed in OHCs. In mice lacking the long isoform, IHCs develop normally but progressively lose the transducing rows of stereocilia (rows 2 and 3). Additionally, these mice suffer profound hearing loss by 9 weeks of age. Remarkably, distortion product otoacoustic emissions (DPOAEs), a measure of OHC function, are unaffected, consistent with an IHC-specific phenotype. The molecular, biochemical and mouse tools we generated provide a strong platform for addressing fundamental questions regarding the function of MYO7A in hair cell MET, particularly in specifying the characteristic differences in MET properties in the two cochlear hair cell types. In Specific Aim 1, we test whether MYO7A is required for hair cell MET. Most models designate MYO7A as a molecular motor integral to the upper tip link density, possibly involved in establishing the mechanical tension important for MET function. However, direct evidence is lacking because knockout and knockdown mouse models of MYO7A have severe defects in hair bundle development. Our long isoform-specific KO mice allow the investigation of MYO7A function in normally developed hair cells. In Specific Aim 2, we will define the enzymatic activities and subcellular localization of MYO7A isoforms in IHCs and OHCs, and then correlate these outcomes with cell type-specific physiological and functional characteristics. Finally, in SA3, we propose to identify cis-and trans-regulatory factors that mediate the cell-type specific expression of MYO7A isoforms. In summary, a novel feature of MYO7A, a well- characterized deafness gene, will enable our exploration of the molecular differences between inner and outer hair cells, an issue of considerable significance for hearing research.
摘要

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Jung-Bum Shin其他文献

Jung-Bum Shin的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Jung-Bum Shin', 18)}}的其他基金

Mechanosensor Proteins in Hair Cell Repair
毛细胞修复中的机械传感器蛋白
  • 批准号:
    10718860
  • 财政年份:
    2023
  • 资助金额:
    $ 16.15万
  • 项目类别:
Split-GFP tagging and live imaging of hair cell proteins
毛细胞蛋白的 Split-GFP 标记和实时成像
  • 批准号:
    10438419
  • 财政年份:
    2022
  • 资助金额:
    $ 16.15万
  • 项目类别:
Split-GFP tagging and live imaging of hair cell proteins
毛细胞蛋白的 Split-GFP 标记和实时成像
  • 批准号:
    10623203
  • 财政年份:
    2022
  • 资助金额:
    $ 16.15万
  • 项目类别:
Significance of Myo7a isoforms in hair cell function
Myo7a 亚型在毛细胞功能中的意义
  • 批准号:
    10032862
  • 财政年份:
    2020
  • 资助金额:
    $ 16.15万
  • 项目类别:
Significance of Myo7a isoforms in hair cell function
Myo7a 亚型在毛细胞功能中的意义
  • 批准号:
    10203919
  • 财政年份:
    2020
  • 资助金额:
    $ 16.15万
  • 项目类别:
Significance of Myo7a isoforms in hair cell function
Myo7a 亚型在毛细胞功能中的意义
  • 批准号:
    10466879
  • 财政年份:
    2020
  • 资助金额:
    $ 16.15万
  • 项目类别:
Significance of Myo7a isoforms in hair cell function
Myo7a 亚型在毛细胞功能中的意义
  • 批准号:
    10684263
  • 财政年份:
    2020
  • 资助金额:
    $ 16.15万
  • 项目类别:
Development of an AAV-CRISPR system for inner ear gene therapy
开发用于内耳基因治疗的 AAV-CRISPR 系统
  • 批准号:
    8765296
  • 财政年份:
    2014
  • 资助金额:
    $ 16.15万
  • 项目类别:
Role of XIRP2 in hair cell function and degeneration
XIRP2 在毛细胞功能和退化中的作用
  • 批准号:
    8957404
  • 财政年份:
    2014
  • 资助金额:
    $ 16.15万
  • 项目类别:
Role of XIRP2 in hair cell function and degeneration
XIRP2 在毛细胞功能和退化中的作用
  • 批准号:
    9748086
  • 财政年份:
    2014
  • 资助金额:
    $ 16.15万
  • 项目类别:

相似海外基金

How novices write code: discovering best practices and how they can be adopted
新手如何编写代码:发现最佳实践以及如何采用它们
  • 批准号:
    2315783
  • 财政年份:
    2023
  • 资助金额:
    $ 16.15万
  • 项目类别:
    Standard Grant
One or Several Mothers: The Adopted Child as Critical and Clinical Subject
一位或多位母亲:收养的孩子作为关键和临床对象
  • 批准号:
    2719534
  • 财政年份:
    2022
  • 资助金额:
    $ 16.15万
  • 项目类别:
    Studentship
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
  • 批准号:
    2633211
  • 财政年份:
    2020
  • 资助金额:
    $ 16.15万
  • 项目类别:
    Studentship
A material investigation of the ceramic shards excavated from the Omuro Ninsei kiln site: Production techniques adopted by Nonomura Ninsei.
对大室仁清窑遗址出土的陶瓷碎片进行材质调查:野野村仁清采用的生产技术。
  • 批准号:
    20K01113
  • 财政年份:
    2020
  • 资助金额:
    $ 16.15万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
  • 批准号:
    2436895
  • 财政年份:
    2020
  • 资助金额:
    $ 16.15万
  • 项目类别:
    Studentship
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
  • 批准号:
    2633207
  • 财政年份:
    2020
  • 资助金额:
    $ 16.15万
  • 项目类别:
    Studentship
The limits of development: State structural policy, comparing systems adopted in two European mountain regions (1945-1989)
发展的限制:国家结构政策,比较欧洲两个山区采用的制度(1945-1989)
  • 批准号:
    426559561
  • 财政年份:
    2019
  • 资助金额:
    $ 16.15万
  • 项目类别:
    Research Grants
Securing a Sense of Safety for Adopted Children in Middle Childhood
确保被收养儿童的中期安全感
  • 批准号:
    2236701
  • 财政年份:
    2019
  • 资助金额:
    $ 16.15万
  • 项目类别:
    Studentship
A Study on Mutual Funds Adopted for Individual Defined Contribution Pension Plans
个人设定缴存养老金计划采用共同基金的研究
  • 批准号:
    19K01745
  • 财政年份:
    2019
  • 资助金额:
    $ 16.15万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Structural and functional analyses of a bacterial protein translocation domain that has adopted diverse pathogenic effector functions within host cells
对宿主细胞内采用多种致病效应功能的细菌蛋白易位结构域进行结构和功能分析
  • 批准号:
    415543446
  • 财政年份:
    2019
  • 资助金额:
    $ 16.15万
  • 项目类别:
    Research Fellowships
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了