The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing
- University of Michigan, United States
- Harvard Medical School, United States
- Stanford University, United States
- National Institute on Deafness and Other Communication Disorders, United States
- University of Michigan Medical School, United States
- University of Kentucky, United States
Abstract
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 through alternative splicing of an N-terminal domain, and that these isoforms selectively traffic to different stereocilia rows. Using an isoform-specific knockout mouse, 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 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.
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Ethics
Animal experimentation: All animal procedures were approved by the institutional animal care and use committees (IACUC) at the University of Michigan (#PRO00004639, #PRO00005913, #PRO00005128), the University of Kentucky (#903M2005) and at the NIDCD (#1263-12).
Reviewing Editor
- Jeremy Nathans, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, United States
Publication history
- Received: May 9, 2015
- Accepted: August 22, 2015
- Accepted Manuscript published: August 24, 2015 (version 1)
- Version of Record published: October 6, 2015 (version 2)
Copyright
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.
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The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing
eLife 4:e08627.
https://doi.org/10.7554/eLife.08627
Further reading
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