PHYSCI 111A Chapter Notes - Chapter 10: Electrophysiology, Antibody, Cdh23
18 Sep 2016
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Document Summary
In this article, grillet and colleagues aim to further demystify mechanotransduction in hair cells on a molecular level; specifically what role the molecule harmonin plays in hair cells beyond development. First, they used immunochemistry and labeling by designing antibodies against the pdz3 domain harmonin to show that it is present below stereocilia tips near upper tip-link density (utld) regions and sparse elsewhere. After determining that the extracellular tip-link filament cdh23 is bound to the pdz2 domain of harmonin they wanted to test if this bond is important for localization. They produced mice that had harmonin unable bind to. Cdh23, due to missense mutations in the pdz2 domain. These differences, especially the change in glg motif interfered with the interaction of harmonin and cdh23, showing a relationship between the two. The mice also had vestibular dysfunction, deafness, and increased auditory thresholds. It was shown that hair bundle development impairment was associated with harmonin delocalization from stereocilia tips.
