Dynamic interaction among proteins in hair cells

毛细胞中蛋白质之间的动态相互作用

基本信息

  • 批准号:
    9527906
  • 负责人:
  • 金额:
    $ 49万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-03-01 至 2019-07-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY The cochlea converts sound waves into electrical signals to convey information to the central nervous system. Highly specialized cells including hair cells, supporting cells and spiral ganglion neurons mediate this operation. Because complex and sophisticated microtubule (MT) networks are needed for the individualized cell shapes and structures required for peripheral signal coding, uncovering the protein networks that modulate MT organization will enrich our understanding of both normal and impaired cochlear physiology. The goal of this proposal is to investigate three largely unexplored proteins, whose functions may be important for the regulation of MTs in the inner ear: CAMSAP3, CDH23-C, and WDR47. CAMSAP3 is a MT minus-end binding protein, while CDH23-C, a cytoplasmic isoform of CDH23, and WDR47, a protein of unknown function, both interact with CAMSAP3. Deletion or mutation of these genes is linked to hearing impairment in humans and in mouse models. Thus, they may potentially be responsible for causing hereditary hearing loss. In AIM I, we investigate the role of CAMSAP3 using conditional knockout mouse models that lack CAMSAP3 in individual cell types in the cochlea including hair cells, supporting cells, and spiral ganglion neurons. We will examine these mice using various anatomical and physiological methods to determine the function of CAMSAP3 in hearing. In AIM II, we investigate the functional consequences of impaired interaction between CDH23-C and CAMSAP3. We will generate a CDH23-C mutant mouse model that mimics the human Usher Syndrome 1D mutation that negatively affects this interaction, and evaluate the importance of the role of CDH23-C in MT regulation via its interaction with CAMSAP3. The experiments are designed to reveal a novel molecular mechanism that involves MT modulation in the cochlea and that is implicated in Usher Syndrome 1D. In Aim III, we investigate the function of WDR47 in hearing through both in vivo and in vitro approaches. We will determine the detailed expression patterns of WDR47 in the cochlea and investigate WDR47's contribution to hearing using WDR47 knockout mice. We will also dissect the molecular basis of interactions between WDR47 and CAMSAP3, and uncover WDR47-associated proteins through both biochemistry and proteomics. Taken together, the proposed studies aim to provide critical information regarding the protein networks that regulate MT organization in the cochlea by focusing on three proteins. Our comprehensive approach utilizes a variety of methods including molecular and cell biology, biophysics, electrophysiology, in vivo physiology and mass spectrometry, thereby allowing us to achieve our goals. The data obtained from the proposed experiments will provide new knowledge about the molecular mechanisms underlying the pathology of hearing loss, and enrich our understanding of the protein networks important for hearing and deafness. This information will guide our current and future efforts in directing treatments and/or in preventing hearing loss.
项目总结

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)

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Jing Zheng其他文献

Jing Zheng的其他文献

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{{ truncateString('Jing Zheng', 18)}}的其他基金

Outer hair cells and noise-induced hearing loss
外毛细胞和噪音引起的听力损失
  • 批准号:
    10862034
  • 财政年份:
    2023
  • 资助金额:
    $ 49万
  • 项目类别:
DYNAMIC INTERATION AMONG PROTEINS IN HAIR CELLS
毛细胞中蛋白质之间的动态相互作用
  • 批准号:
    8297956
  • 财政年份:
    2012
  • 资助金额:
    $ 49万
  • 项目类别:
DYNAMIC INTERATION AMONG PROTEINS IN HAIR CELLS
毛细胞中蛋白质之间的动态相互作用
  • 批准号:
    8620644
  • 财政年份:
    2012
  • 资助金额:
    $ 49万
  • 项目类别:
DYNAMIC INTERATION AMONG PROTEINS IN HAIR CELLS
毛细胞中蛋白质之间的动态相互作用
  • 批准号:
    8431347
  • 财政年份:
    2012
  • 资助金额:
    $ 49万
  • 项目类别:
DYNAMIC INTERATION AMONG PROTEINS IN HAIR CELLS
毛细胞中蛋白质之间的动态相互作用
  • 批准号:
    9022461
  • 财政年份:
    2012
  • 资助金额:
    $ 49万
  • 项目类别:
Preventing hair cell loss by regulating prestin's function
通过调节 prestin 的功能来防止毛细胞损失
  • 批准号:
    7933797
  • 财政年份:
    2009
  • 资助金额:
    $ 49万
  • 项目类别:
Preventing hair cell loss by regulating prestin's function
通过调节 prestin 的功能来防止毛细胞损失
  • 批准号:
    7827241
  • 财政年份:
    2009
  • 资助金额:
    $ 49万
  • 项目类别:
Investigating the nature of prestin-associated proteins
研究 prestin 相关蛋白的性质
  • 批准号:
    7211417
  • 财政年份:
    2005
  • 资助金额:
    $ 49万
  • 项目类别:
Investigating the nature of prestin-associated proteins
研究 prestin 相关蛋白的性质
  • 批准号:
    7020704
  • 财政年份:
    2005
  • 资助金额:
    $ 49万
  • 项目类别:
Investigating the nature of prestin-associated proteins
研究 prestin 相关蛋白的性质
  • 批准号:
    6923414
  • 财政年份:
    2005
  • 资助金额:
    $ 49万
  • 项目类别:

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