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Molecules of mechanotransduction. Cadherin 23 and protocadherin 15 interact to form tip-link filaments.

机译:机械转导的分子。钙黏着蛋白23和原钙黏着蛋白15相互作用形成末端连接长丝。

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摘要

Hair cells of the inner ear are mechanosensors that transduce mechanical forces arising from sound waves and head movement into electrochemical signals to provide our sense of hearing and balance. Mechanoelectrical transduction takes place close to the tips of stereocilia in proximity to extracellular tip-link filaments thought to gate mechanosensitive ion channels. In the first chapter of this thesis I present evidence that cadherin 23 (CDH23) and protocadherin 15 (PCDH15) interact to form tip links. In the second chapter I demonstrate that specific cleavage of CDH23 protein in a knock-in mouse model affects mechanotransduction. The studies presented define the molecular composition of tip links and provide evidence for their direct involvement in mechanotransduction. Other projects I participated in are described in the appendices. In brief, our team established that CDH23 interacts with the PDZ adaptor protein harmonin (Appendix 1) and that harmonin is a component of upper tip-link densities where it participates in establishing the sensitivity of hair bundles to mechanical stimulation (Apendix 3). We also studied the role of PCDH15 in the development of stereociliary bundles (Appendix 2).
机译:内耳的毛细胞是机械传感器,可以将声波和头部运动产生的机械力转换为电化学信号,以提供我们的听觉和平衡感。机电转导发生在接近于纤毛末端的地方,靠近细胞外的尖端连接细丝,这些细丝被认为是对机械敏感离子通道的门。在本论文的第一章中,我提供了钙粘蛋白23(CDH23)和原钙粘蛋白15(PCDH15)相互作用形成末端连接的证据。在第二章中,我证明了敲入小鼠模型中CDH23蛋白的特异性裂解会影响机械传导。提出的研究定义了尖端连接的分子组成,并为其直接参与机械转导提供了证据。附录中描述了我参与的其他项目。简而言之,我们的团队确定了CDH23与PDZ衔接蛋白harmonin相互作用(附录1),并且harmonin是上部尖端连接密度的组成部分,在其中它参与建立发束对机械刺激的敏感性(附录3)。我们还研究了PCDH15在立体纤毛束形成中的作用(附录2)。

著录项

  • 作者

    Kazmierczak, Piotr.;

  • 作者单位

    The Scripps Research Institute.;

  • 授予单位 The Scripps Research Institute.;
  • 学科 Biology Molecular.;Biology Cell.;Biology Neuroscience.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 233 p.
  • 总页数 233
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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