Harmonin Mutations Cause Mechanotransduction Defects in Cochlear Hair Cells
| Autor: | Rachel A. Dumont, Ulrich Müller, Peter G. Gillespie, Concepción Lillo, Edith Hintermann, Anna Sczaniecka, Takashi Sato, David S. Williams, Nicolas Grillet, Wei Xiong, Piotr Kazmierczak, Martin Schwander, Bechara Kachar, Anna Reynolds |
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| Rok vydání: | 2009 |
| Předmět: |
Neuroscience(all)
Stereocilia (inner ear) HUMDISEASE Protocadherin Cell Cycle Proteins Cell Surface Extension Biology Mechanotransduction Cellular Models Biological MOLNEURO Article 03 medical and health sciences 0302 clinical medicine CDH23 Hearing otorhinolaryngologic diseases medicine Animals Humans Mechanotransduction Adaptor Proteins Signal Transducing 030304 developmental biology 0303 health sciences Hair Cells Auditory Inner Cadherin General Neuroscience Cell biology Cytoskeletal Proteins medicine.anatomical_structure CELLBIO Cell Surface Extensions sense organs Hair cell 030217 neurology & neurosurgery PCDH15 |
| Zdroj: | Neuron. 62:375-387 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2009.04.006 |
| Popis: | SummaryIn hair cells, mechanotransduction channels are gated by tip links, the extracellular filaments that consist of cadherin 23 (CDH23) and protocadherin 15 (PCDH15) and connect the stereocilia of each hair cell. However, which molecules mediate cadherin function at tip links is not known. Here we show that the PDZ-domain protein harmonin is a component of the upper tip-link density (UTLD), where CDH23 inserts into the stereociliary membrane. Harmonin domains that mediate interactions with CDH23 and F-actin control harmonin localization in stereocilia and are necessary for normal hearing. In mice expressing a mutant harmonin protein that prevents UTLD formation, the sensitivity of hair bundles to mechanical stimulation is reduced. We conclude that harmonin is a UTLD component and contributes to establishing the sensitivity of mechanotransduction channels to displacement. |
| Databáze: | OpenAIRE |
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