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.
Document Type
Article
Publication Date
8-24-2015
Digital Object Identifier (DOI)
http://dx.doi.org/10.7554/eLife.08627
Funding Information
National Institute on Deafness and Other Communication Disorders (NIDCD)
DC000039-18
-Thomas B Friedman -Inna A Belyantseva -Jonathan E Bird
National Institute on Deafness and Other Communication Disorders (NIDCD)
DC000048-18
-Thomas B Friedman
-Inna A Belyantseva
-Jonathan E Bird
Hearing Health Foundation (HHF)
N/A
-Mirna Mustapha
University of Michigan (U-M)
N/A
-Qing Fang
National Institute on Deafness and Other Communication Disorders (NIDCD)
DC05053
-Qing Fang
-Artur A Indzhykulian
-Mirna Mustapha
-Gregory I Frolenkov
-Sally A Camper
National Institute on Deafness and Other Communication Disorders (NIDCD)
DC008861
-Artur A Indzhykulian
-Gregory I Frolenkov
National Institute on Deafness and Other Communication Disorders (NIDCD)
DC05188
-David F Dolan
Repository Citation
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.; and Bird, Jonathan E., "The 133-kDa N-Terminal Domain Enables Myosin 15 to Maintain Mechanotransducing Stereocilia and Is Essential for Hearing" (2015). Physiology Faculty Publications. 65.
https://uknowledge.uky.edu/physiology_facpub/65
Figures and figure supplements
Notes/Citation Information
Published in eLife, v. 4, article e08627, p. 1-22.
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.