NDLI: The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing

Content Provider	PubMed Central
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.
Editor	Nathans, Jeremy
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 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.
Related Links	http://dx.doi.org/10.7554/elife.08627
Starting Page	8627
File Format	PDF
ISSN	2050084X
e-ISSN	2050084X
Journal	eLife
Volume Number	4
Language	English
Publisher	eLife Sciences Publications, Ltd
Publisher Date	2015-08-01
Access Restriction	Open
Rights Holder	eLife Sciences Publications, Ltd
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology

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The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing

Data from: Mechanotransduction current is essential for stability of the transducing stereocilia in mammalian auditory hair cells (Dataset)

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The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing

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The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing

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The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing