Hair cells are specialized mechanoreceptor cells that are responsible for converting mechanical energy to electrochemical signals. They are distributed across the animal kingdom, from certain invertebrates (e.g., sea anemones) to mammals. Hair bundles, the mechanoreceptor apparatus of hair cells, are composed of stereocilia interconnected by extracellular linkages, including tip links. Tip links are critical to mechanotransduction as a part of a gating spring, or to lie in series with a gating spring. Tip links are composed of cadherin 23 (CDH23) and protocadherin 15 (PDCH15). The interactions between tip links, polypeptides forming the mechanotransduction channel and any accessory polypeptides are not known. In Chapter 1, experimental results are detailed in which CDH23 interacts dynamically with an unknown protein via a specific extracellular domain in sea anemone. Such interactions are critical to maintaining normal structure and function of the anemone hair bundle.
Damage to hair cells, which leads to abnormal vestibular function and hearing loss, is an important health issue. Unfortunately, repair of hair cells in mammals is limited, and mammals have little to no capacity for replacing lost hair cells. On the other hand, sea anemones have a marked capability to repair hair bundles. Secreted proteins, named repair proteins (RPs), enriched in mucus coating tentacles, enhance hair bundle repair. Intriguingly, anemone-derived RPs also enhance repair of traumatized hair cells in the lateral lines of blind cavefish. In order to understand the mechanism underlying this remarkable repair activity, protein components of RPs must be identified. In Chapter 2, 37 polypeptides in RPs were identified using a proteomics approach. Among these polypeptides were two heat-shock proteins (HSPs) and 10 polypeptide subunits of 20S proteasomes. Experiments confirmed that biologically active HSP70 and proteasomes are required to repair damaged hair bundles. In Chapter 3, the efficacy of RPs was tested in mammalian auditory hair cells. Encouragingly, mechanotransduction was restored and the structural integrity of traumatized hair bundles was improved in murine outer hair cells after 1-hr treatment in anemone RP-enriched culture media. These results raise the possibility of treating damaged hair cells by exogenously supplied RPs.
|Advisor:||Watson, Glen M.|
|Commitee:||Chlan, Caryl A., Heller, Stefan, Mire, Patricia L., Smith, Karen M.|
|School:||University of Louisiana at Lafayette|
|Department:||Environmental and Evolutionary Biology|
|School Location:||United States -- Louisiana|
|Source:||DAI-B 76/12(E), Dissertation Abstracts International|
|Subjects:||Audiology, Cellular biology, Physiology|
|Keywords:||Cochlea, Hair cell, Mouse, Repair, Sea anemone, Trauma|
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