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The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing
The precise assembly of inner ear hair cell stereocilia into rows of increasing height is critical for mechanotransduction and the sense of hearing. Yet, how the lengths of actin-based stereocilia are regulated remains poorly understood. Mutations of the molecular motor myosin 15 stunt stereocilia g...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592939/ https://www.ncbi.nlm.nih.gov/pubmed/26302205 http://dx.doi.org/10.7554/eLife.08627 |
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author | Fang, Qing Indzhykulian, Artur A Mustapha, Mirna Riordan, Gavin P Dolan, David F Friedman, Thomas B Belyantseva, Inna A Frolenkov, Gregory I Camper, Sally A Bird, Jonathan E |
author_facet | Fang, Qing Indzhykulian, Artur A Mustapha, Mirna Riordan, Gavin P Dolan, David F Friedman, Thomas B Belyantseva, Inna A Frolenkov, Gregory I Camper, Sally A Bird, Jonathan E |
author_sort | Fang, Qing |
collection | PubMed |
description | The precise assembly of inner ear hair cell stereocilia into rows of increasing height is critical for mechanotransduction and the sense of hearing. Yet, how the lengths of actin-based stereocilia are regulated remains poorly understood. Mutations of the molecular motor myosin 15 stunt stereocilia growth and cause deafness. We found that hair cells express two isoforms of myosin 15 that differ by inclusion of an 133-kDa N-terminal domain, and that these isoforms can selectively traffic to different stereocilia rows. Using an isoform-specific knockout mouse, we show that hair cells expressing only the small isoform remarkably develop normal stereocilia bundles. However, a critical subset of stereocilia with active mechanotransducer channels subsequently retracts. The larger isoform with the 133-kDa N-terminal domain traffics to these specialized stereocilia and prevents disassembly of their actin core. Our results show that myosin 15 isoforms can navigate between functionally distinct classes of stereocilia, and are independently required to assemble and then maintain the intricate hair bundle architecture. DOI: http://dx.doi.org/10.7554/eLife.08627.001 |
format | Online Article Text |
id | pubmed-4592939 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-45929392015-10-06 The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing Fang, Qing Indzhykulian, Artur A Mustapha, Mirna Riordan, Gavin P Dolan, David F Friedman, Thomas B Belyantseva, Inna A Frolenkov, Gregory I Camper, Sally A Bird, Jonathan E eLife Cell Biology The precise assembly of inner ear hair cell stereocilia into rows of increasing height is critical for mechanotransduction and the sense of hearing. Yet, how the lengths of actin-based stereocilia are regulated remains poorly understood. Mutations of the molecular motor myosin 15 stunt stereocilia growth and cause deafness. We found that hair cells express two isoforms of myosin 15 that differ by inclusion of an 133-kDa N-terminal domain, and that these isoforms can selectively traffic to different stereocilia rows. Using an isoform-specific knockout mouse, we show that hair cells expressing only the small isoform remarkably develop normal stereocilia bundles. However, a critical subset of stereocilia with active mechanotransducer channels subsequently retracts. The larger isoform with the 133-kDa N-terminal domain traffics to these specialized stereocilia and prevents disassembly of their actin core. Our results show that myosin 15 isoforms can navigate between functionally distinct classes of stereocilia, and are independently required to assemble and then maintain the intricate hair bundle architecture. DOI: http://dx.doi.org/10.7554/eLife.08627.001 eLife Sciences Publications, Ltd 2015-08-24 /pmc/articles/PMC4592939/ /pubmed/26302205 http://dx.doi.org/10.7554/eLife.08627 Text en http://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (http://creativecommons.org/publicdomain/zero/1.0/) . |
spellingShingle | Cell Biology Fang, Qing Indzhykulian, Artur A Mustapha, Mirna Riordan, Gavin P Dolan, David F Friedman, Thomas B Belyantseva, Inna A Frolenkov, Gregory I Camper, Sally A Bird, Jonathan E The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing |
title | The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing |
title_full | The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing |
title_fullStr | The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing |
title_full_unstemmed | The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing |
title_short | The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing |
title_sort | 133-kda n-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592939/ https://www.ncbi.nlm.nih.gov/pubmed/26302205 http://dx.doi.org/10.7554/eLife.08627 |
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